Recent research has demonstrated that psoriasis is not the result of a keratinocyte disorder, as previously believed. Although the exact etiology has not been clearly defined, much data has accumulated to elucidate the role of the immune system, particularly T lymphocytes, in the pathogenesis of the disease. With this knowledge, a number of biologic therapies that specifically target key pathogenic events have been developed. Efalizumab, a recombinant humanized monoclonal IgG1 antibody, is a T-cell modulator approved for patients with moderate to severe chronic plaque psoriasis. This article reviews the role of T lymphocytes in psoriasis pathogenesis, the mechanism of efalizumab action, and the efficacy and safety data observed during the efalizumab clinical trials.