Patients developing fever in neutropenia are at high risk of infection-related complications. Their outcome is influenced by the degree of severity (sepsis, severe sepsis and septic shock). Sepsis describes clinical syndromes resulting from systemic inflammatory response. Diagnosis of sepsis is based on simple clinical criteria. Treatment of neutropenic patients with sepsis does not differ from sepsis treatment in non-neutropenic patients. A variety of treatment options have failed (e.g. anti-cytokine strategies, anti-endotoxin antibodies), however, in recent years successful targeted treatment, the use of activated protein C or the substitution of hydrocortisol has been shown to reduce mortality rates. The outcome of neutropenic sepsis is influenced by the underlying disease as well, however survival rates of neutropenic patients treated on the intensive care unit have improved during the past decade. This paper focuses on pathophysiology, diagnosis and treatment of sepsis. Evidence based medicine (EBM) criteria are used to grade treatment recommendations [50].