Progression of HIV infection is largely dependent on the interaction between the viral factors and host factors. HIV primarily infects the CD4 lymphocytes in the body. It brings about the destruction of CD4 cells through multiple mechanisms including apoptosis. The loss of CD4 cell population ultimately leads to the inability of infected person to deal with opportunistic organisms. Host genetic factors such as HLA polymorphism and HIV co-receptor polymorphism may influence either susceptibility to infection or disease progression. Innate immune mechanisms may play a role in disease progression. However, adaptive immune response is the most critical component of immune system for control of HIV infection. HIV-specific CD4 helper response and HIV-specific CTL responses have clearly emerged as the most important host factors that may decide the rate of disease progression. However, the role of neutralizing antibodies still remains to be understood in context with the disease progression. One of the gray areas is the role of mucosal immune response in HIV infection. However, it is clear that it is not a single component but orchestrated action of different immune mechanisms will decide the outcome of HIV infection. The studies in persons exposed to HIV infection but who are uninfected and the long term non-progressors will be critical for understanding the immunopathogenesis of HIV infection.