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OBJECTIVE The present research examines locus of control, self esteem and perceived social support as psychosocial variables assumed to moderate psychological adjustment. DESIGN Cross sectional design. PLACE AND DURATION OF STUDY The research was conducted during 2012 - 2013 at various schools including special schools as well as vocational centres, hospitals and rehabilitation centres in Karachi. SUBJECTS AND METHODS It includes a sample of 200 adolescents including 100 adolescents with disabilities (40 blind, 34 deaf and 26 physically disabled) and 100 adolescents without disabilities. A demographic information form and four self report measures assessing locus of control, self esteem, perceived social support and psychological adjustment were completed by all the participants. RESULTS All explanatory variables in the proposed model for the research were found to be significant using regression analysis resulting in the acceptance of the hypothesis [F3,196=43.388,p<.001]. CONCLUSION The final model suggests a strong association between the predictors and the criterion variable with unidirectional effects of self esteem towards psychological adjustment affecting both adolescents with and without disabilities. The results suggest a strong need for developing psychological interventions, based mainly on self esteem along with locus of control and the perception of support, for all adolescents in order to boost Their overall adjustment. [ABSTRACT FROM AUTHOR]