HIV-1 is a retrovirus with a complex genetic structure. The virus particle is composed of the RNA genome, structural core (Gag) proteins, enzymatic core (Pol) proteins, and structural envelope (Env) proteins. Virus infection is regulated by the expression of its receptor, CD4, on lymphocytes and macrophages. This involves specific interactions between domains of the envelope protein and CD4, and perhaps additional factors. The life cycle involves reverse transcription from the viral RNA into DNA, which may be integrated into the host chromosomal DNA. Expression of the integrated viral genome leads to an array of spliced and unspliced RNA products which encodes the virion proteins, as well as viral proteins that regulate diverse aspects of the virus life cycle. Different steps in virus entry, replication and assembly are potential targets for antiviral development. Genetics approaches have been applied in many ways for development of HIV-1 therapeutics. Analysis of sequence heterogeneity has identified specific mutations associated with drug resistance. HIV-1 nucleic acids provide valuable measures for quantitation and characterization of HIV-1 infection in infected individuals. Gene therapies are also underway and directed at HIV-1 infection.