A wide variety of different immunologic approaches have been evaluated as potential therapies for HIV disease. Whether any of these approaches will play a role in clinical management will require the completion of the appropriate clinical trials. Importantly, all clinical trials present opportunities to evaluate aspects of the pathogenesis of HIV infection that are perhaps unevaluable in vitro. Clinical trials of antiretroviral drugs have defined the dynamics of HIV replication [37,38]. The complexities and heterogeneity of the immune system and particularly its responses to HIV are being unveiled in the setting of clinical trials of immune-based therapies. Truly effective treatments for HIV will result in long-term preservation of immune function allied to control of virus replication in infected individuals. Immune-based therapy might well play a significant role in such strategies.