Sepsis is among the most common reasons for admission to ICUs throughout the world, and it is believed to be the third most common cause of death in the United States. The pathogenetic mechanism and physiologic changes associated with sepsis are exceedingly complex, but our understanding is evolving rapidly. The major pathophysiologic changes in patients with septic shock include vasoplegic shock (distributive shock), myocardial depression, altered microvascular flow, and a diffuse endothelial injury. These pathophysiologic changes play a central role in the management of sepsis. The early management of patients with severe sepsis and septic shock centers on the administration of antibiotics, IV fluids, and vasoactive agents, followed by source control. However, the specific approach to the resuscitation of patients with septic shock remains highly controversial. This review provides a practical and physiologic-based approach to the early management of sepsis and explores the controversies surrounding the management of this complex condition.