Moderate to severe plaque psoriasis has traditionally been treated with agents that have toxicities associated with long-term use. Many patients therefore cannot be treated safely, conveniently or effectively with traditional therapies. Recent phase 3 clinical trials for efalizumab, a biological agent targeted specifically at the T-cell-based pathology of psoriasis, have demonstrated its short- and long-term efficacy and safety for the treatment of psoriasis. This article reviews results from 12-week, six-month, and three-year trials, focusing on the drug's safety, efficacy, and therapeutic response time, as well as the phenomenon of rebound in non-responding patients. Efalizumab emerges as an important addition to the dermatological pharmacopeia for the long-term treatment of psoriasis.