The 1990s have been marked by tremendous progress in understanding HIV-1 infection and disease progression in infected individuals. The new discoveries have direct applications in predicting clinical outcomes and monitoring antiviral therapies. With the identification of secondary receptors for HIV-1 cell entry, the CCR-5 receptor was found to be a single genetically determined factor influencing both HIV-1 transmission and disease progression. Quantitation of HIV-1 RNA led to the discoveries that detectable or even high levels of HIV-1 replication occur during all phases of infection, and that plasma HIV-1 RNA levels are powerful predictors of clinical outcome. These findings have increased the ability to predict disease progression and to monitor-antiviral therapy in infected individuals.