The serum bactericidal test (SBT) has been used for almost 40 years to monitor therapy in patients with bacterial endocarditis, osteomyelitis, and other serious infections. The SBT is basically a variation of the broth dilution test adapted to assess the activity of a treated patient's own serum against the infecting microorganism. Only recently, however, have rigorous attempts been made to standardize all the relevant variables that affect results of the SBT. The widely recommended goal of a peak bactericidal titer of 1:8 in the therapy for infective endocarditis may be inadequate for the treatment of some patients. Peak titers of 1:64 or greater in the microdilution SBT should be sought if they can be achieved without toxicity. Titers of less than 1:8 may be acceptable, although they are less often successful, if serious toxicity would result from increased dosage. Peak SBT titers of 1:8 or greater yield high cure rates for acute osteomyelitis in children; data are limited in adults. A defined SBT method is necessary for additional multicenter clinical trials on which firmer recommendations for its future use can be made.