Viruses have evolved to become highly efficient at nucleic acid delivery to specific cell types while avoiding immunosurveillance by an infected host. These properties make viruses attractive gene-delivery vehicles, or vectors, for gene therapy. Several types of viruses, including retrovirus, adenovirus, adeno-associated virus (AAV), and herpes simplex virus, have been modified in the laboratory for use in gene therapy applications. Because these vector systems have unique advantages and limitations, each has applications for which it is best suited. Retroviral vectors can permanently integrate into the genome of the infected cell, but require mitotic cell division for transduction. Adenoviral vectors can efficiently deliver genes to a wide variety of dividing and nondividing cell types, but immune elimination of infected cells often limits gene expression in vivo. Herpes simplex virus can deliver large amounts of exogenous DNA; however, cytotoxicity and maintenance of transgene expression remain as obstacles. AAV also infects many nondividing and dividing cell types, but has a limited DNA capacity. Alternatively, chimeric viral-vector systems that combine advantageous properties of two or more viral systems are also being explored. Although viral-mediated gene delivery has proved to be the most efficient means of gene transfer, nonviral means are also under development. Many of these nonviral systems incorporate portions of viral vectors to increase the efficiency of gene delivery or expression. Retrovirus, adenovirus, and AAV vectors are being evaluated currently in several Phase 1 clinical trials for treatment of diseases such as cancer, cystic fibrosis, Gaucher disease, and arthritis.