Cotton is an important commercial crop of global importance. Cotton is known as the backbone of Pakistan’s economy. Cotton leaf curl virus disease (CLCuVD) is a serious threat to the successful cotton production and is transmitted by whitefly Bemisia tabaci Gennadius under field conditions. A disease and vector predictive model based on 5 years epidemiological factors was developed and validated based on 2 years epidemiological factors for the prediction of CLCuVD and its vector. Y= 145+ 4.47x 1 -0.151x 2 -0.490x 3 -1.83x 4 +1.58x 5 -4.84x 6 R 2 = 0.79 (Five years data) Y= 145+ 2.78x 1 - 0.998 x 2 -0.400 x 3 -1.02 x 4 +3.85 x 5 -2.25 x 6 R 2 = 0.75 (Two years data) Where y = CLCuVD, x 1 = Minimum temperature, x 2 = Rainfall, x 3 = Relative humidity, x 4 = Wind velocity, x 5 = Whitefly, x 6 = Maximum temperature. Y= 57.0 - 0.370x 1 - 0.0853x 2 -0.297x 3 +0.813x 4 -0.565x 5 R 2 = 0.64 (Five years data) Y= 27.5-0.726x 1 -0.511x 2 -0.122x 3 -0.177x 4 +0.639 x 5 R 2 = 0.58 (Two years data) Where y = Whitefly, x 1 = Maximum temperature, x 2 = Minimum temperature, x 3 = Relative humidity, x 4 = Rainfall, x 5 = Wind velocity. A significant (P<0.05) but negative correlation was observed between maximum temperature and CLCuVD. The value of the coefficient of correlation was observed in the following order: 2006 (r=0.80*) < 2004 (r=0.79*) < 2005 (r=0.76*) <2002 (r=0.61*) and < 2003 (r=0.60*). Except 2006, the relationship of CLCuVD with rainfall was found non- significant during the subsequent years (r < 0.47). Wind velocity was found non- significant but negatively correlated with CLCuVD. Whitefly had significant and positive correlation with CLCuVD during all the five years. The relative humidity contributed significantly in the build up of whitefly population during 2005 only (r=0.60). During rest of the years relative humidity did play a prominent role in the spread of this vector as was evident from the value of correlation coefficient 0.34 ≤ r ≤ 0.47. The wind velocity did not contributed as effectively as compared to other variables. None of the screened varieties/advanced lines was found to be immune against cotton leaf curl virus disease and varied greatly in response to disease incidence during both the years (2007-08). Only three varieties/advanced lines (NIBGE-2, PB-899, NIAB- 884) were found to be highly resistant against CLCuVD. Eight cultivars (BH-162, NIAB- 824, CIM-496, MJ-7, CIM- 446, CIM-473, VH-148, Alseemi hybrid) were found to be resistant. Six varieties/advanced lines (NIAB-111, PB- 897, FH-2925, CIM-438, CIM-497, FH-115) were found moderately resistant. Five cultivars (FH-900, CIM-707, CIM-506, FH-901, CIM-498,) were observed to be moderately susceptible and five varieties/advanced lines (PB-843, FH-1000, BH-163, CIM-482, CIM-443) exhibited susceptible response. Five varieties/advanced lines (CIM-534, FH-2000, FH-2006, MNH-732, S-12) were found to be highly susceptible against cotton leaf curl disease, respectively. All the treatments reduced whitefly population and CLCuVD incidence significantly compared to untreated control. Azadirachta indica (Neem) extract was the most active to manage the B. tabaci population. Salicylic acid was at number second and Eucalyptus globules (Sufaida) was at number third whereas Allium sativum (Garlic) and Calotropics procera (Ak, Akund) were at number four and fifth respectively in managing the B. tabaci and CLCuVD. Aloe babadensis (Aloe) and Datura stramonium (Datura) were found less effective compared to other treatments.