Septicemia, as defined by the clinical response to a severe systemic infection, remains an important clinical problem associated with substantial morbidity and mortality rates. Treatment of septicemia has three facets. One is to restore and maintain cardiovascular stabilization by the use of fluids and vasoactive agents. The second is to eradicate the source of infection with the appropriate antibiotics and drainage of the septic focus whenever possible, and the third is to limit an excessive immunologic host response to infection. Monoclonal antibodies to endotoxin may be helpful in septicemia due to gram-negative organisms, although the definitive proof of their efficacy is debated. Anti–tumor necrosis factor antibodies and interleukin-1 receptor antagonist are under trial, as well as other forms of therapy likely to control an excessive host response to the invading agent. It is probable that a combination of therapies will reduce the septicemia-related morbidity and mortality rates.