The natural history of human immunodeficiency virus (HIV) infection is marked by a progressive deterioration of the host immune system and a concomitant increase in host viral burden. The rationale for major HIV disease staging systems is discussed in light of this natural history. The need for early diagnosis and treatment of HIV-infected patients is underscored by the prolonged phase during which patients are simultaneously asymptomatic and infectious. Clinical, immunologic, and virologic markers of disease stage, progression, and response to therapy will require continuing refinement as we better understand the pathobiology of HIV disease.