Human immunodeficiency virus (HIV) infection is now recognized as a chronic illness. An estimated 33 million people are infected with HIV worldwide. With the advent of highly active antiretroviral therapy (HAART), HIV-1 infection is now manageable as a chronic disease in patients who have access to medication and who achieve durable virologic suppression. Since the drugs cannot eradicate the virus, cure is not yet possible, and patients have to maintain a lifelong adherence with the risk of toxic effects, drug-drug interactions and drug resistance. A clear understanding of the viral replication and its interaction with host cell factors has led to the development of a large number of effective antiretroviral drugs (ARVs). New drugs in the existing class such as apricitabine, elvucitabine and etravirine have shown promising results against HIV isolates resistant to first line drugs. These drugs have offered a new choice for patients with drug resistant disease. However, the impact of their long term use on safety is yet to be assessed. Novel drugs with unique mechanism of action such as CD4 receptor attachment inhibitors, maturation inhibitors, pharmacokinetic enhancers, capsid assembly inhibitors and lens epithelium derived growth factor inhibitors are still under development. Currently, ARVs, especially tenofovir and emtricitabine, are also being evaluated for prevention of sexual transmission of HIV-1. The initial results of an HIV prevention trial network are encouraging and have recommended the use of ARVs for pre-exposure prophylaxis. Thus, ARVs form the key component of HIV prevention and treatment strategy.