Psoriasis is a chronic T-cell-mediated inflammatory disease of the skin and joints that affects 1-3% of the world population. Conventional treatments for moderate to severe psoriasis are associated with broadband immunosuppression and/or organ toxicities that can be problematic when used long term. Advances in the understanding of psoriasis pathogenesis have led to targeted therapy in the form of biologics. These agents have gained popularity as safe, effective, and convenient alternatives for the treatment of chronic, moderate to severe plaque psoriasis. This review will focus on the five main biologics used in the treatment of moderate to severe plaque psoriasis: efalizumab, alefacept, etanercept, infliximab and adalimumab. Mechanisms of action, guidelines for usage, efficacy data, and safety concerns will be discussed for each biologic. In addition, the new Th17 biologics and their role in psoriasis pathogenesis will also be examined.