The immunopathogenic mechanisms underlying human immunodeficiency virus (HIV) disease are extremely complex; the disease process is multifactorial with multiple overlapping phases. Viral burden is substantial and viral replication occurs throughout the entire course of HIV infection. Inappropriate immune activation and elevated secretion of certain cytokines compound the pathogenic process. Profound immunosuppression ultimately occurs together with a disruption of the microenvironment of the immune system, which is probably unable to regenerate spontaneously. Thus, therapeutic strategies in HIV disease must not be unidimensional, but rather must be linked to the complex pathogenic components of the disease and must address where feasible each of the recognized pathogenic processes for the possibility of therapeutic intervention.