Individuals with moderate-to-severe psoriasis perceive that the disease exerts profound emotional, social and physical effects on their lives, and a significant percentage report that they do not consider their treatment sufficiently aggressive. A survey of individuals with a variety of chronic diseases reveals that those with psoriasis have the lowest estimation of their health-related quality of life, lower than that of patients with arthritis, congestive heart failure, chronic lung disease or depression. Although psoriasis can be treated effectively, many treatments are associated with long-term risks. Toxicity-sparing treatment strategies that include combination, rotational and sequential regimens can help to control moderate-to-severe psoriasis while reducing risk. Algorithms for the treatment of moderate-to-severe psoriasis detail possible options for specific types of psoriasis and for patients with specific needs. The purpose of the algorithms is to make optimum use of phototherapy, traditional cytotoxic and immunosuppressive agents, retinoids, and newer biologic agents.