DURING THE 15 YEARS since the publication by Anderson and Keefer on the results of penicillin therapy, a powerful and bewildering array of antibiotic agents has emanated from the pharmaceutical industry. With further contributions now being made by the molecular manipulation of the basic structures of old agents, the physician must more than ever make a clear decision on whether antibiotic therapy for an individual patient is necessary at all. The purpose of this paper is to relate the practical usefulness of various natural and semisynthetic penicillin compounds one to another. No attempt is made to give a comprehensive account of the therapeutic use of penicillin or to define the situations in which antibiotic treatment may be indicated. Although laboratory studies can define an impressive spectrum of activity in vitro, or an impressive increase in plasma concentrations after administration, the final assessment of the value of an antibiotic requires extended