Erythroderma can be caused by a variety of underlying dermatoses, infections, and systemic diseases. Many of the findings on history, physical examination, and laboratory evaluation are nondiagnostic. Distinctive clinical and laboratory features pointing to a specific disease may be evident, however. Conclusive clinicopathologic correlation may require multiple and repeated skin biopsies. The prognosis of erythroderma has improved with the advent of innovative dermatologic therapies (e.g., cyclosporine and synthetic retinoids) and advances in the management of systemic manifestations. Death from sepsis, cardiac failure, adult respiratory distress syndrome, and capillary leak syndrome continue to be rarely reported. A high index of suspicion for these complications must be maintained to facilitate early medical intervention.