Psoralens and sunlight have been used by the Egyptians and Indians for hundreds of years for the treatment of vitiligo. The combination of oral psoralens and artificial ultraviolet A (PUVA) therapy was approved for the management of severe psoriasis by the Food and Drug Administration in 1982. Since then PUVA therapy has been found to be an effective modality in the treatment of many cutaneous conditions. When properly administered, the major short-term side effects are minimal. The long-term side effects may include an increased risk of squamous cell carcinoma, atypical cutaneous pigmentation, accelerated skin aging, and ophthalmologic abnormalities. By careful patient selection and limiting the cumulative UVA dosage and frequency by using combinations or alternative therapies, these side effects may be reduced. Continued reporting of carefully carried out long-term prospective studies will provide us with more knowledge of the long-term side effects of PUVA. In the meantime, for each patient on PUVA therapy the risk/benefit ratio should be carefully considered.