HIV infection is regarded as one of the most important causes of mortality disease worldwide. The pathogenesis of HIV infection is complex and a multi-factorial process that is influenced by both viral and host factors. These factors play an important role in disease progression in HIV infected people. The HIV infected individuals eventually develop AIDS in a different progressive rate. The biological correlates to progression rate toward AIDS remain to be elusive. A variety of factors including host genetic susceptibility, immune function, viral genetic variability and coinfections with several microbial agents may affect the rate of progression of infection. This chapter provides information on most important factors that regulate the rate of progression of HIV infection toward AIDS.