The introduction of new penicillins, such as methicillin, cloxacillin, oxacillin, and nafcillin, and of the cephalosporin compound, cephalothin, to clinical medicine has offered appropriate agents for treating staphylococcal infections. Variations in pharmacology and antibacterial activity have created a need to regulate their administration with more concern than when giving benzylpenicillin. Guidelines for using these agents in the treatment of staphylococcal infections, by both parenteral and oral formulations, have been presented. In addition to staphylococcal infections, some less well known, gram negative organisms are causing a significant number of hospital-acquired wound infections and other complications in surgical patients. Variability in the results of antibiotic-sensitivity tests is discussed, and the relationship of therapeutic doses of antibiotics to single-disc sensitivity test results is explained. The necessity for careful sensitivity-test determinations in these difficult infectious problems is stressed. In addition, several examples of the predictable toxicity or the side effects of potent antibiotics have been presented, and some guidelines for preventing serious sequellae from the use of these agents are provided.