The cephalosporins are the largest and most diverse family of antimicrobial agents available. Although they rarely are considered drugs of first choice for the therapy of bacterial infections, they are the most commonly prescribed agents for both ambulatory and hospitalized patients. The first-generation agents have the most limited spectrum of bactericidal activity, but they are the most potent against Gram-positive microbes. The third- and fourth-generation agents have a broad spectrum of activity that includes the majority of Gram-negative pathogens. However, they are less active than their first-generation counterparts against Gram-positive bacteria, especially S aureus. The cephalosporins generally are well tolerated, and the oral agents are palatable. However, their use is limited by increasing resistance among certain groups of bacteria and high cost, especially of the parenteral and recently licensed oral agents. The prudent physician need not be familiar with all cephalosporins, but should be knowledgeable about a select few.