Publisher Summary This chapter discusses the transmission, pathogenesis, and epidemiology of HIV. Several papers have come up that highlight the neurological manifestations of AIDS. Many different therapies are under investigation for HIV infections with several nucleoside analogues being evaluated. Those nucleoside analogues prepared as anti-HIV agents are targeted against the unique virus enzyme, reverse transcriptase (RT). In clinical studies, azidothymidine (AZT) decreased mortality and the frequency of opportunistic infections and to some extent reverses neurological symptoms. AZT produces bone marrow toxicity leading to anemia; this toxicity can now be evaluated in vitro. A proposed explanation for this toxicity involves a buildup of thymidine monophosphate (dT-MP) by competitive inhibition of thymidylate kinase by AZT-MP. In an uncontrolled clinical trial, ribavirin, administered orally, gave a transient clinical improvement associated with HIV suppression. Also oral ribavirin treatment, at escalating doses, for at least one month, inhibited RT activity with acceptable toxicity and appeared to inhibit HIV replication. Ribavirin antagonises the effect of pyrimidine nucleosides but enhances the inhibitory effects of purine nucleosides. While the structures and in vitro biological data for a number of compounds related to buciclovir (BCV) appear similar, the in vivo biological activity differs widely. Biochemical and pharmacokinetic parameters that may account for this discrepancy have been discussed in this chapter.