Much progress has been made in developing new and more efficient treatments for human immunodeficiency virus (HIV) infection, the cause of acquired immunodeficiency syndrome (AIDS). However, the scope of the HIV epidemic and the limitations of existing treatments necessitate the continued development of novel treatment strategies. Gene therapy is one such forward-looking strategy. Gene therapy approaches for HIV infection include efforts to interfere with viral replication directly by engineering HIV-resistant cells or indirectly by eliminating infected cells from the body, primarily by eliciting a therapeutic immune response to destroy HIV-infected cells. Although the prospect of gene therapy as a routine treatment for HIV infection remains distant, continuous progress is being made, which should also have implications for gene therapy strategies for a variety of other diseases. This article reviews some of the strategies for investigating the feasibility of gene transfer for the treatment of HIV infection.