With the rapid scale-up of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Several new safe antiretroviral, and newer class of drugs and monitoring assays are developed recently. As a result the treatment guideline for the management of HIV disease continue to change. This review focuses on evolving science on Indian policy--antiretroviral therapy initiation, which drugs to start with, when to change the initial regimen and what to change.