Human immunodeficiency virus (HIV-1) encodes proteins essential to its replication cycle. Reverse transcriptase, protease, and viral envelope gp120 are three proteins that have been targeted for antiviral drug development. Eleven inhibitors of reverse transcriptase, seven inhibitors of protease, and one inhibitor of viral envelope binding have been approved for use. Antiretroviral therapy has reversed the mortality rate of HIV-infected persons, but over time, therapy-resistant virus variants may outgrow. A large body of information is now available to relate specific amino acid sequences in the resistant variants to specific drug regimens. Designing therapy to compensate for virus resistance results in improved patient outcomes. The advent of microsequencing technologies paved the way for direct sequencing of DNA products generated by polymerase chain reactions, thus dramatically lowering the cost of HIV gene sequencing. Designing therapy according to genetic analysis of HIV variants will not only also improve clinical outcome, but will also deter the transmission of drug-resistant strains.