Third-generation cephalosporins are important additions to the range of antibiotics available for treating children with serious bacterial infections. They are highly active against the common pathogens, which cause bacterial meningitis in children. Strains of Haemophilus influenzae type b resistant to both ampicillin and chloramphenicol, and Streptococcus pneumoniae relatively resistant to penicillin remain susceptible to cefotaxime and ceftriaxone. Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, as well as the other more common gram-negative bacilli isolated from neonates and children are susceptible to these agents. However, Listeria monocytogenes is not cephalosporin-sensitive. Ceftazidime is the only third-generation cephalosporin useful for treating serious infections due to Pseudomonas aeruginosa in children. As with other beta-lactam antibiotics, the clearance of cephalosporins is prolonged in neonates, particularly premature babies. Cefotaxime and ceftriaxone are equivalent to ampicillin and chloramphenicol for the treatment of bacterial meningitis in children over two to three months of age with respect to neurologic outcome and safety, despite the in vitro activity of cefotaxime and ceftriaxone being much greater than the standard antibiotics for the meningeal pathogens. Cefotaxime and ceftriaxone are effective in the treatment of serious gram-negative infections in children. In many instances, ceftriaxone can be administered once daily, which allows for more convenient therapy, particularly on an outpatient basis. Although controversial, ceftazidime has been used as single-agent therapy for empiric treatment of neutropenic immunocompromised children with fever. © 1990.