Dramatic changes in the methods of obtaining blood cultures in clinical practice have recently occurred owing to factors such as the rising number of patients at risk for infection, "newer" pathogens occurring in the bloodstream, widespread use of indwelling intravascular devices, and our improved ability to recover and identify microorganisms in blood. Guidelines for the "proper" practice of obtaining blood cultures are needed. Blood cultures must be obtained under sterile conditions when there is suspicion of bacteremia/ mycobacteremia, fungemia, or viremia. This review provides recent information on optimal blood culture practices during suspected bloodstream infection in hospitalized patients including those with continuous or intermittent bacteremia, patients with intravascular devices, and compromised hosts such as immunodeficient patients and those in intensive care units. The traditional two-bottle system of aerobic and anaerobic cultures continues to be helpful, although the frequency of anaerobic bacteremia has decreased. More recently, special culture/transport media have become available for the recovery of mycobacteria, fungi, and viruses. Communication between the clinician and laboratory personnel frequently aids in improving the yield from blood cultures. (Arch Intern Med. 1994;154:841-849)