Since the mid-1970s there has been a number of advances in blood culture practices and technology; these advances have been based largely on well-designed controlled clinical evaluations of blood culture systems and media. Thus, a sound scientific basis for the fundamental principles of blood culturing now exists. In this article, I will address issues of clinical and technical importance with regard to blood culturing; these issues include skin antisepsis, the number and timing of blood cultures, the appropriate volume of blood for culture, culture media and additives, length and atmosphere of incubation, and interpretation of positive blood culture results. Finally, I will discuss the currently available blood culture systems, with an emphasis on the newer continuous-monitoring blood culture systems.