After identification of HIV in 1980, it affects the world more than 30 million people. The background of HIV infection is Immune system failure and various immunological phenomena associated with virus infection. Quite observation brings out fundamental understanding of how virus affects various T cells and its cell compartments. Many Novel targets for the management of HIV infection have become increasingly relevant in view of extensive drug resistance, side effects and high pill burden of conventional anti-retroviral agents. X-ray crystallography, nuclear magnetic resonance, and mass spectrometry have lead to the identification of novel class of drugs targeting new stages of HIV life cycle. This class of agents has its ability to target their individual site to suppress the HIV replication. Despite this, new developments providing hope to patients and clinicians in the fights against HIV and its eradication of the disease even though it is still remains elusive. This review explores the issues surrounding the development of these new agents and their active target sites.