Cephalosporin antibiotics are bactericidal against most gram-positive cocci and gram-negative bacilli of clinical importance. They are relatively nontoxic but like the penicillins may cause hypersensitivity reactions. Agents with clinically advantageous pharmacokinetics include cefazolin, moxalactam, and cefadroxil. First-generation cephalosporins are indicated for surgical prophylaxis and for treatment of most staphylococcal and streptococcal infections in patients who are allergic to penicillins. Activity against gram-negative bacilli increases from first- to third-generation drugs, but sensitive isolates should be treated with first-generation agents to prevent resistance to newer cephalosporins and to minimize the expense for the patient. Treatment of Bacteroides fragilis and Pseudomonas aeruginosa infections is not entirely satisfactory with currently available agents. No cephalosporin is active against the enterococci, and superinfection with these organisms has occurred during treatment with moxalactam. Some experimental cephalosporins have improved activity against P. aeruginosa and gram-negative bacilli that are resistant to multiple drugs. A few of these agents have a very long half-life. It is likely that cephalosporin antibiotics will continue to proliferate.