Erythrodermic psoriasis (EP) is the most severe form of psoriasis. Although it may develop de novo, it is most commonly associated with long-standing, active disease. EP develops acutely or following a subacute or chronic course. The erythrodermic phase is dominated by generalized erythema and scaling that can be accompanied by an inability to maintain homeostatic functions, a potentially life-threatening complication. Management of EP is difficult and medication should be administered not only to treat psoriasis but also to treat the erythrodermic syndrome and extracutaneous complications. The therapies that are available to treat EP include traditional systemic drugs (such as methotrexate, acitretin, and cyclosporine) and the biological agents (such as etanercept, infliximab, adalimumab, and ustekinumab), which can be used as monotherapy or as part of combined therapy. Clinical experience of treating these disorders with biological agents is limited. As there is a lack of high-quality comparative studies, the best choice of treatment agent must be based on a combination of the patient’s clinical presentation and comorbidities. Generally speaking, when rapid control of an erythrodermic crisis is needed, as in patients with unstable psoriasis, fast-acting agents such as infliximab and cyclosporine may be the best choice. In patients with less acute EP, methotrexate (which has a slower onset of action) administered as monotherapy or combined with biological agents, can be useful. In addition, acitretin should also be considered for treating patients who are infected with HIV or are otherwise immunocompromised, or those with stable erythrodermic psoriasis. Adv Psoriasis Inflamm Skin Dis 2011;2(3):119–25.