The treatment of severe sepsis and septic shock remains a challenge as we approach the next millennium. Although more attention is being given to guidelines and care pathways for sepsis, these are unfortunately based primarily on consensus opinion. Additional research into supportive interventions in this potentially devastating disease is needed. Priorities in the management of sepsis include rapid reversal of hypotension and hypoperfusion, followed by empiric antibiotic therapy and definitive localization and treatment of infection nidus. A wide variety of adrenergic agents may be useful in sepsis. Initial therapy for hypoperfusion, however, should be targeted toward establishing adequate intravascular volume and left ventricular preload. Adjunctive therapy to prevent complications during the intensive care unit stay is important.