Despite several decades of research and phenomenal advances in technology and therapeutics, sepsis remains a catastrophic enigma. As a frequent cause of death, sepsis now rivals acute myocardial infarction. The longstanding therapeutic principles of early antibiotics use and supportive care have been difficult to improve upon. The authors conducted a concise review of pertinent literature on the pathophysiologic mechanisms of sepsis and the pharmacologic effects of statins. They conclude that, though statins possess anti-inflammatory and lipid-lowering properties, these effects may not be advantageous throughout the changing immunoresponse that can occur in sepsis syndrome. Based on the available information, statin therapy seems advantageous before the onset of sepsis and during sepsis resolution—but not during the compensatory anti-inflammatory response that may occur. Thus, the authors recommend that, until the status of a patient’s changing immune response can be clearly determined, the uninterrupted use of statin therapy throughout the full spectrum of sepsis should be avoided.