Sepsis is a common and critical illness diagnosed via blood culture. Although a continuous blood culture monitoring system was introduced several decades ago, optimal utilization and improvement of blood culture methods has not been discussed recently. The author describes several blood culture-related topics including optimal blood collection procedures, quality control indicators, prior antibiotic treatment, delayed entry, time to detection, follow-up blood culture, catheter-related bloodstream infection, and new techniques to rapidly identify microorganisms. Although rapid, automatic blood culture systems are likely to be developed in the near future, quality improvement should be accomplished by well-educated medical personnel. (Ann Clin Microbiol 2013;16:153-161)