Sepsis is the body’s systemic response to infection and is a serious health care concern that affects neonatal, pediatric, and adult populations worldwide. Severe sepsis (sepsis that has progressed to cellular dysfunction and organ damage or evidence of hypoperfusion) and septic shock (sepsis with persistent hypotension despite adequate fluid resuscitation) are still associated with high mortality rates despite improvements in the management of infectious processes. The cellular processes that occur as a result of the inflammatory response in sepsis, including impaired perfusion and microcirculatory coagulation, can lead to organ system dysfunction. Early recognition of sepsis can help prompt treatment to improve patient care. Current pediatric guidelines emphasize early recognition, aggressive fluid resuscitation, and administration of antibiotics within the first hour for a better outcome. The practitioner needs to always be mindful of the possibility of sepsis when examining a patient with potential symptoms.