Psoriasis is a lifelong, incurable disease that normally develops before the age of 30 years and affects approximately 1.4% of the Spanish population. Numerous clinical trials have demonstrated the efficacy of efalizumab, a recombinant, humanized, monoclonal antibody, which has been approved for the treatment of moderate-to-severe plaque psoriasis. However, clinical trials do not necessarily reflect routine clinical practice because they are conducted under controlled conditions and in specific populations. In this paper, we describe our experiences at a large University Hospital in Spain using efalizumab to manage patients with psoriasis. We found that patients who respond to treatment at week 12 usually demonstrate long-term disease control with continuous use of efalizumab. Early response may be easiest to achieve in patients with extensive body surface area (BSA) involvement and low Psoriasis Area and Severity Index (PASI) scores for erythema, induration and desquamation. However, evaluation of treatment success after 12 weeks may be premature in patients with moderate or low BSA involvement if they have clinically significant PASI scores for erythema, induration and desquamation. In our experience, the safety profile is good and patients appreciate the convenience of efalizumab compared with other interventions.