With the advent of biological therapies for the treatment of plaque psoriasis, guidance on the usage of these new agents has become necessary. One such agent, efalizumab, a humanized recombinant monoclonal IgG(1) antibody developed to target T-cell-mediated inflammation, provides rapid and sustained efficacy for many psoriasis patients. This article explores the pretreatment, initiation, and treatment phases with efalizumab therapy. In the pretreatment phase, physicians need to assess patients' disease state and educate them about the course of efalizumab treatment. Prior to initiation, physicians need to establish stable disease, ensure an adequate transition or washout of any prior psoriasis therapeutics, and obtain baseline platelet counts. After initiating treatment, both physician and patient must participate in disease monitoring. Patients responding favourably may receive continuous treatment. Those who do not respond to the drug or who experience adverse events should be managed appropriately in order to continue therapy or be transitioned onto another agent. A growing body of clinical evidence, as well as experience from clinical investigators, has provided much insight into the management strategies for patients undergoing treatment with efalizumab.