Traditional systemic therapy for psoriasis is limited by either lack of efficacy or the long-term side effect profile of the medications used. Newer information about the pathophysiology of the disease has led to new perspectives on developing novel techniques for attacking psoriasis. This article discusses the pathogenesis of psoriasis, looks at the immunologic factors that contribute to forming a psoriatic plaque, reviews how novel biologic therapies are made, and explores how biologics can target each of these specific parts of the immunologic cascade.