Momordica charantia (bitter gourd) is among one of the most liked vegetable in world because of its medicinal and nutritive value. Its‟ per hectare yield in Pakistan is much lower than its neighboring countries like China and India. Among various management factors diseases play a major role in low yield. Among the diseases Myrothecium leaf spot (MLS) has been noticed as emerging threat for bitter gourd and other cucurbits. Before initiating for the project investigation, a small scale survey was conducted to investigate disease severity and distribution pattern and for designing of structured questionnaire in collaboration with Pest Warning & Quality Control of Pesticides wing, Punjab, Lahore, and Ayub Agriculture Research Institute Faisalabad. Survey area of the Punjab province was divided into Various zones viz Rice Zone, Cotton Zone, Mixed Cropping Zone, Thal Zone, Barani (Rain fed) Zone and DG Khan zone as described by PARC (Pakistan Agricultural Research Council) zonal allocation system. These zones vary significantly with respect to climate soil, and crop management strategies. Disease index for the survey period ranged 25-30% According to 0-5 visual disease severity Scale (VSRS) disease severity ranged 1-4 on for mixed cropping zone while in DG Khan it ranged from 0-2 during the surveyed years. Cultivation of vegetable in tunnels makes it more susceptible because fungal inoculums and availability of alternate host make situation worst. Myrothecium roridum strain Mr 10 (accession # FCBP 1155) was deposited in first fungal culture bank, Pakistan and M. roridum strain Mr 37 (accession # DSM 28971) in Leibniz-Institute-DSMZ, Germany. Virulence of Myrothecium roridum population was evaluated against commercial variety “Jaunpuri” @ 1 x 105spore concentration under pot and field conditions. Out of the 54 test isolates, 23 were highly, 17 moderately and 14 were less aggressive and none fall under Avirulent category. The size of spore ranged in length from 5-8 μm and in width to 1.4-1.8μm. Physiological attributes influencing radial growth and subsequently conidia and sporodochia production of M. roridum were analyzed. PDA medium was found best to support the mycelia growth followed by BGA medium. M. roridum produced circular, flat colonies with floccose texture and filiform margins on PDA at 25 °C. The highest radial growth was observed at pH 5.0 followed by pH 5.5 with 16/8 h light/darkness period at 30 °C whereas sporodochia production was highest at 35 °C. Genetic variation among the test isolates, 13 primers were selectedfor RAPD amplification which produced 93 bands in test isolates. Out of 93 DNA fragments, 28% were monomorphic whereas 72% were polymorphic bands. The isolates Mr31 and Mr54 collected from Faisalabad and DG Khan made a clear subgroup A (genetic distance = 0.68). Similarity of M. roridum isolates originated from distant agro-ecological zones may be due to active movement of infected germplam. The attempts were made to understand interaction of M. roridum with M. charantia. Conidial germination and emergence of germ tube was observed on light microscope while combination of light, transmission electron and fluorescent microscope, germ tube emergence was observed after 6 hours and directly penetrate the host cells. Hyphae and conidia were seen in leaf veins beyond point of infection, leading to assumption that fungus is able to use vascular system for transmission within host. Susceptibility reaction of M. charantia commercial cultivars and candidate lines was investigated in pot and field experiments under natural environmental conditions. During early growth stages there was great similarity in symptomatic development of infection expressions whereas on later stages of plant growth trend of infection development changed under pot and field conditions. The potted plant exhibited 75-90 days life cycle and higher mortality at fruiting stage. Whereas under field conditions no plant mortality was recorded and plant life span was 110-130 days. Under field conditions different growth stages of the plant can be seen on the same time but highest susceptibility was observed at flowering and fruit formation stage. The spectrum of resistance was more clearly defined on potted plants rather than field. Under field conditions, varieties Cross 888 f1 hybrid, Long green, Jhalri, JK Leena, BG-7107, PKBT-1, BSS-616, VRBG 233 and Fsd long exhibited moderately resistant reaction. In case of susceptible varieties sensitivity was higher at flowering and fruiting stages. Management strategies adopted for Integrated Disease Management (IDM) revealed that Allium sativum inter-cropping lowered disease incidence (63 %), suppressed pathogen at 6-8 leaf stage and remained effective till harvesting while Curcuma longa (11 % under greenhouse and 5 % in field) and Colocasia esculenta (9 % in pots and 8 % in field) were least effective. Variation in mode of action of extracts on physiological response was recorded on macroscopic characters colony color, texture, margins, spore production and elevation. Nicotiana plumbaginifolia and Parthenium hysterophorus extracts revealed to inhibit the colony radial growth and possess significant antifungal activity against M. roridum under in vitro conditions. Chemical application intensity for vegetable crops is much higher than on field crops and same is true for M. roridum. Among the test commercial fungicides, Antracol at 0.05% and 0.1% significantly reduced the mycelia growth. In general systemic fungicides Antracol, Score and Cabrio top proved most effective against Mr37 isolate. Tested fungicides proved effective in the present study but could not completely inhibit the M. roridum growth. Tebuconazole cytotoxicity was evaluated and resulted in complete inhibition of spore germination at 5 mg/L whereas significantly reduced the germ tube emergence and mycelium elongation at 0.5 and 1.5 mg/L concentrations under in vitro conditions. Collected data was subjected to appropriate statistical analysis to measure the significance (P < 0.05) of results, including student‟s t-test, analysis of variance (ANOVA) followed by Tukey‟s HSD and Pearson correlation. It is concluded that areas apparently looking disease free or exhibiting lesser disease index are because of newly adapted bitter gourd cultivation trend and climatic conditions are suitable for the cultivation of susceptible but high yielding varieties. Candidate lines including MONIKA(7004), LEENA(7005), CBT-36, and cultivars VRBG 233 and Green wonder showed stable resistance during germplasm screening. Local resources like, Nicotiana plumbaginifolia and Parthenium hysterophorus plant extracts along with the inter-cropping of Allium plants could provide effective management of disease in pathogen prevailing areas.