The clinical management of neutropenic infections represents a great diagnostic and therapeutic challenge. Established sepsis criteria only partially reflect the neutropenic setting. Diagnostic procedures are frequently impaired by thrombocytopenia and progressive respiratory insufficiency. Increased tendency to bleed, engraftment, and fulminant progression represent major therapeutic challenges. Thus, crucial for the diagnosis and therapy of neutropenic sepsis are clear and well-communicated algorithms, rapid action, and close collaboration between oncologists and intensivists.