When bacteremia is suspected, the physician's first step is to determine the most likely source by using all available data from the history, physical examination, and laboratory studies. When evaluation for bacteremia is warranted, two or three sets of blood cultures should be carefully obtained using strict procedure guidelines, and empirical antibiotic therapy should be initiated. If the source of bacteremia has not been identified, blood culture results must be correlated with the clinical situation so that further investigations may be pursued and antimicrobial therapy may be initiated or modified. A high index of suspicion must be maintained for unusual or fastidious pathogens in immunocompromised patients.