AIDS (HIV) and hepatitis B viruses are remarkably similar in their sharing of reverse transcription, in their ancestral origins and common genetic elements, and in their modes of transmission. Both are hypermutable and exist as quasispecies due primarily to errors in reverse transcription, though there is severe restriction in the replicative competence of most hepatitis B mutants. They differ in the lack of an integrase in hepatitis B virus and in their pathogenesis in the infected host. HIV survives mainly by antigenic variability, immune evasion, and impairment of immune function though viral regulatory control elements seek to restrict fatal damage to the host. Hepatitis B virus survives primarily by mutation of e antigen/core genes that directly obviates cytotoxic T cell destruction of infected liver cells, or indirectly limits destruction of infected cells through induction of anergy in the cytotoxic T cell response. Most persons infected with hepatitis B virus recover completely while recovery from HIV infection is rare if ever. Hepatitis B is highly preventable by vaccine while HIV vaccine is still seeking a meaningful immunoprophylactic target. AIDS and hepatitis B represent an extreme example, among the viruses of man, in their close similarities but distinct differences. In depth details and perspectives are presented in this review.