Cefotaxime has been used extensively in many pediatric centers in the United States for the past 10 or more years. Its main usage has been for the treatment of various serious bacterial infections in pediatric patients, primarily meningitis and sepsis. It has also been used to treat intraabdominal, urinary tract, soft tissue, bone, and joint infections. Although there has been a marked reduction in the incidence of invasive Haemophilus influenzae type b infections following the introduction of effective vaccines, cefotaxime remains very useful against the other common pathogens causing serious infections in pediatric patients. The increasing number of pneumococci resistant to penicillin and third-generation cephalosporins has created a new challenge for the management of serious pneumococcal infections. In many institutions, cephalosporins in general have been overused and abused, resulting in the emergence of resistant organisms and an increasing burden on resources. The judicious use of cefotaxime and other cephalosporins should be emphasized.