For years, quantitative blood cultures found only limited use as aids in the diagnosis and management of septic patients because the available methods were cumbersome, labor intensive, and practical only for relatively small volumes of blood. The development and subsequent commercial availability of lysis-centrifugation direct plating methods for blood cultures have addressed many of the shortcomings of the older methods. The lysis-centrifugation method has demonstrated good performance relative to broth-based blood culture methods. As a result, quantitative blood cultures have found widespread use in clinical microbiology laboratories. Most episodes of clinical significant bacteremia in adults are characterized by low numbers of bacteria per milliliter of blood. In children, the magnitude of bacteremia is generally much higher, with the highest numbers of bacteria found in the blood of septic neonates. The magnitude of bacteremia correlates with the severity of disease in children and with mortality rates in adults, but other factors play more important roles in determining the patient's outcome. Serial quantitative blood cultures have been used to monitor the in vivo efficacy of antibiotic therapy in patients with slowly resolving sepsis, such as disseminated Mycobacterium avium-M. intracellulare complex infections. Quantitative blood culture methods were used in early studies of bacterial endocarditis, and the results significantly contributed to our understanding of the pathophysiology of this disease. Comparison of paired quantitative blood cultures obtained from a peripheral vein and the central venous catheter has been used to help identify patients with catheter-related sepsis and is the only method that does not require removal of the catheter to establish the diagnosis. Quantitation of bacteria in the blood can also help distinguish contaminated from truly positive blood cultures; however, no quantitative criteria can invariably differentiate contamination from bacteremia.