HIV disease is a chronic infection that requires lifelong treatment with the aim of suppressing the circulating viral load in order to improve the host immune status. The development of safe and effective antiretroviral agents with unique resistance profiles or novel mechanisms of action are an important goal for the long-term management of HIV-infected patients. The antiretroviral drug classes include entry and fusion inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors. Current antiretroviral therapeutic regimens are associated with the emergence of issues like HIV drug resistance, drug toxicities, associated poor patient adherence to therapy, co-existence of other opportunistic, and blood borne viral infections. Newer antiretroviral agents may provide some alternatives to modulate the therapy as per the requirements of the HIV infected patients.