Third-generation cephalosporins are broad-spectrum antimicrobial agents useful in a variety of clinical situations. No one cephalosporin is appropriate for all infectious disease problems. Cefotaxime and ceftizoxime have the best gram-positive coverage of the third-generation agents. Ceftazidime and cefoperazone are the only third-generation drugs that provide antipseudomonal coverage. Ceftriaxone's long half-life allows for once-daily dosing, making ceftriaxone an excellent drug for outpatient antibiotic therapy of community-acquired infections. Ceftriaxone is also useful for the treatment of Lyme disease and sexually transmitted diseases. The third-generation cephalosporins except for cefoperazone penetrate cerebrospinal fluid and are indicated for the treatment of bacterial meningitis. Their proven record of clinical efficacy, favorable pharmacokinetics, and low frequency of adverse effects make third-generation cephalosporins the preferred antibiotic in many clinical situations.