There has been significant progress in the last few years in demonstrating the utility of recombinant viral vectors in treating a variety of ocular diseases. The field has moved beyond 'proof-of-principle' and, in fact, has entered the phase where some of these vectors/paradigms are being or soon will be evaluated in human clinical trials. For this reason and also, to increase the understanding of immunological effects of transgenes/viral vectors on the eye, it is important to summarize what is known about these effects. Here, the biology of and immune responses to intraocular injection of three different recombinant viral vectors - adenovirus, adeno-associated virus (AAV), and lentivirus - are summarized. Perhaps, in part because of the unique immunological environment of the eye, the immunological effects of these viruses appear to be fairly benign. Nevertheless, a significant cell-mediated immune response can develop after intraocular administration of adenovirus. The magnitude of this response is affected by the nature of the intraocular compartment to which this virus is administered. Neither AAV nor lentivirus, however, elicit a cell-mediated response and are thus promising vectors for treatment of chronic ocular (retinal) diseases.