Fever can be described as a coordinated rise in temperature in response to infectious and noninfectious causes, which varies with the anatomical site. This adaptive heat shock response has been conserved for millions of years in vertebrates. Elevated temperature stimulates and optimizes innate and adaptive immune responses. In addition, most microorganisms have shown thermal stress-related growth inhibition, and in vitro data indicate that β-lactam antibiotics in particular appear to have significantly improved susceptibility profiles in the presence of fever-range temperatures. Despite these favorable effects of fever, many physicians consider fever a harmful event that should be treated without discrimination of the underlying cause. Observational studies have indicated that attempts to lower the temperature in patients with sepsis are associated with increased mortality. This article aims to summarize the most relevant results of the existing clinical data and provide the clinician with guidance on how to manage fever in patients with sepsis.