Neutropenic fever is a common and potentially life-threatening condition in patients treated for cancer. Rapid initiation of appropriate antimicrobial therapy is necessary to decrease the risk of mortality. Most infections are due to gram-positive organisms, but the mortality rate is higher for gram-negative infections. Multidrug-resistant organisms are an emerging threat to neutropenic patients. Increasing data suggest that the pathophysiology of neutropenic fever and neutropenic sepsis is substantially different from non-neutropenic fever and sepsis. Additional research is needed to both further elucidate the pathogenesis of neutropenic fever and to develop additional effective antimicrobials.