As the field of human gene therapy has developed over the past 15 years, T-cell immunodeficiencies have been a frequent target of investigation (Table 1). The first of these was adenosine deaminase (ADA) deficiency (severe combined immunodeficiency [SCID]) because of the availability of the responsible gene. As the genes responsible for several of the other T-cell immune deficiencies have been identified and cloned, these deficiencies also have been investigated in preclinical studies, and are now the subject of clinical trials. This article reviews the work that has been performed to date and future directions.