For many years, the mainstays of psoriasis therapy were conventional oral immunosuppressants (eg, cyclosporine and methotrexate) and retinoids. Recently, six biologic agents were approved for the treatment of psoriasis in Canada and the United States: alefacept, efalizumab, etanercept, infliximab, adalimumab, and ustekinumab. Biologic agents exert their therapeutic effect in psoriasis through inhibition of various pathways. Although these treatments are new to the management of psoriasis, many have been used in other disease states, such as rheumatoid arthritis, psoriatic arthritis, and Crohn's disease. Long-term safety data are available from the treatment of these diseases. Both conventional and biologic treatments are effective in the treatment of psoriasis, but they are associated with serious adverse events, ranging from organ toxicity to serious infections, birth defects, and malignancies. This article reviews the safety profiles of both classes of treatments.