During the last decade, the survival of patients with fever and neutropenia has continued to improve. This is largely a reflection of the increasing repertoire of antimicrobial agents available to treat the fevers and infections that arise in this ever-increasing population of patients. Although it would be optimal if therapeutic decisions could always be made based on the microbial isolates and their sensitivity patterns, this is generally not possible in the cancer patient. Fever remains the predominant manifestation of infection, but the underlying microbial etiology is infrequently delineated. In spite of improved diagnostic tests, clinical acumen along with vigilant and repetitive patient assessment remain the cornerstone for evaluation of the cancer patient who becomes febrile. Indeed, strict adherence to simple principles can have a significant impact on improving the chances for survival of cancer patients who develop fever or infection.