Despite substantial advances in antimicrobial therapy, infection remains a major cause of morbidity and mortality in immunocompromised cancer patients. As more intensive, curative antineoplastic treatment regimens are established, the risk for fatal infectious complications will continue to rise. Signs and symptoms of infection in this compromised population may be subtle; yet, an undetected and untreated infection can quickly evolve into septic shock and death. Typically, fever is considered to be a clinical hallmark of infection. Yet, most patients initially present to the clinical setting with a fever of unknown origin. Given the lethal nature of infections in immunocompromised patients, one must assume that the febrile patient is infected until proven otherwise.