Technologies for transfer of exogenous genes into primary T cells have been limited until recently. The introduction of new approaches for gene transfer via different viral vectors has expanded the options for genetic manipulation of primary T cells and has provided powerful tools for studies of T cell activation and differentiation. We provide a brief overview of the systems currently available and contrast the advantages and disadvantages of each. We also describe a new transgenic model that enables highly efficient gene delivery into primary T cells by nonreplicating adenoviral vectors.