We know that human immunodeficiency virus (HIV) is an important pandemic of modern generation causing large death toll worldwide. India is also no exception with 2.12 million people already affected by HIV. The only way to reduce morbidity and mortality due to HIV is antiretroviral therapy (ART). But a high degree of adherence is critical for the effectiveness of ART, and non-adherence is associated with an overall poor outcome in HIV patients. We conducted a randomized controlled prospective study to find out the factors responsible for non-adherence to ART and to assess the role of cognitive behavioral therapy (CBT) to improve adherence. In this study, 60 HIV/AIDS patients with non-adherence (< 95% adherence) were randomized into two groups consisting of 30 patients each, one group (intervention) was administered structured CBT and the other group (control) was put on standard therapy. Factors responsible for non-adherence were overconcern about side effects (33%), polarized thinking (27%), mind reading (27%), and magnification (20%).