Efalizumab is a novel immunomodulator that blocks T-cell migration and activation. The drug was initially approved in October 2003 for the treatment of adult patients with chronic moderate to severe plaque psoriasis. This review will discuss the efficacy and safety data for efalizumab in the treatment of psoriasis. In clinical use, efalizumab has utility as a first-line biologic therapy for plaque psoriasis, as well as a first-line choice for hand and foot psoriasis, overweight patients, and those who have had inadequate response to a TNF inhibitor. In addition, several off-label applications of efalizumab will be reviewed.