Extracorporeal photochemotherapy has been used for almost three decades for the treatment of several T-cell-mediated diseases, and its efficacy has been proven in few well-designed controlled randomized trials. However, to date, there are no reliable data on a hypothetic dose-effect, optimal rhythm of administration, drug interactions, or the "pharmacokinetics" and "pharmacodynamics" of this cell therapy. In particular, it is not clear whether ECP gains to be used in combination with immunosuppressive or immunomodulative drugs. In the future, clinical trials may address these issues in order to clarify the most beneficial use of a cell therapy which absence of toxicity is uniformly recognized.