Fever is defined as a rectal temperature greater than 38.0°C (>100.4°F). A recently documented fever at home should be considered the same as a fever in the ED and should be managed similarly. All febrile infants younger than 28 days should receive a “full sepsis workup” and be admitted for parenteral antibiotic therapy. Clinical and laboratory criteria can be used to identify a low-risk population of febrile infants aged 1 to 4 months who have not received 2 doses of conjugate vaccines for bacterial meningitis. Children with sickle cell disease are at high risk and require special evaluation. MRSA infections are now common and should be considered in all patients with pyoderma, severe pneumonia, and catheter-related sepsis. HSV infection of the CNS should be considered whenever a patient has altered mental status and CSF findings are not diagnostic of bacterial meningitis. Fever rarely represents life-threatening pathology; however, a handful of less common serious causes of pediatric fever exist with the potential for morbidity and mortality.