Efalizumab (anti-CD11a), a targeted T cell modulator, is a humanized monoclonal antibody being studied for plaque psoriasis. Phase I and II studies demonstrated that efalizumab treatment results in histologic improvement and clinical benefit in patients with moderate to severe disease. Phase III clinical trials confirmed the clinical activity and safety of weekly efalizumab. Efalizumab is associated with a rapid onset of clinical benefit, with significant improvements observed as early as 4 weeks. Extending treatment from 12 to 24 weeks both maintains and improves the initial responses achieved at 12 weeks. Both 12 and 24 weeks of efalizumab therapy were generally well tolerated. Ongoing studies are being conducted to further define the optimal dosing and administration schedules for efalizumab in patients with moderate to severe plaque psoriasis.