Murine monoclonal antibodies specifically directed at the CD3 molecular complex are widely used in clinical transplantation. They are potent inhibitors of immune function and may be administered in association to conventional immunosuppressants. The main purpose of this review is to summarize our present knowledge on the CD3 molecule, to discuss the available data on the clinical use of anti-CD3 MAb (therapeutic effectiveness, mode of action and side effects) and the recent information derived from the use of anti-CD3 MAb in experimental models that are opening new perspective in the applications of anti-CD3 and will hopefully lead to the extension of its clinical use to settings different from transplantation.