The alternative conceptions of students are very important in determining the nature of science education in our schools. The purpose of this study was to investigate the alternative conceptions of students about “Energy”, “Living”, and “Chemical Change” and to assess the effectiveness of instructional strategies for changing students’ conceptions. During first phase of the study alternative conceptions of 267 students of 6th, 8th, and 10th classes from four Government high schools of Quetta were investigated through Interview about Instances (IAI) approach. The information about socioeconomic background, age and family of the sample students were also collected during the interview. The alternative conceptions of the sample students about ‘energy’, ‘living’, and ‘chemical change’ were found to be similar to alternative conceptions held by students of different nationalities / regions as reported in international research literature. The socio economic background of students did not appear to have any relation with their alternative conceptions. Similarly, no significant differences were found in the alternative conceptions of the students of different ages or classes. In the second phase, a two-tier conceptual-diagnostic “paper and pencil” test in Urdu language was developed to assess the alternative conceptions of students about the selected science concepts. This test was later used as posttest. Third phase of the study assessed the effectiveness of proposed instructional strategies. Sixteen (16) science teachers of two experimental schools were given training about instructional strategies in a training workshop. The science teachers of experimental and control group schools taught the related chapters of the textbooks in their respective classes. 25% students of class 9 of the experimental and control group schools were given the posttest. It was found that the alternative conceptions of the experimental group students about Energy, Living, and Chemical Change, were similar to the alternative conceptions of the control group students. The hypothesis that alternative conceptions of experimental group students were closer to scientists’ concepts, than those of control group students, was not proven. The findings of this study have significant implications for investigating the alternative conceptions of science teachers about teaching and learning; approaches to teaching; and the classroom instructional practices. The findings call for developing and using diagnostic techniques to elicit students’ alternative conceptions and for developing a repertoire of context based effective instructional strategies. It was recommended that science teachers should be involved in impact assessment process of their professional development activities and be encouraged to improve their instructional approaches to achieve desired conceptual changes among their students.