O riginally developed based on research completed in the early 1940s by Professor Giuseppe Brotzu, the cephalosporins have sustained their position as a very significant class of antibiotics worldwide, comprising over one half of the available -lactam antibiotics. Brotzu first discovered cephalosporin compounds produced by the fungal organism Cephalosporium acremonium. He isolated the fungus from sewage seawater in Calgiari, Sardinia, after he observed a natural pattern of periodic clearing of microbes from a local harbor area. Brotzu subsequently tested filtrates from C. acremonium cultures, observing antimicrobial activity against infections in animals and humans, including the injection of filtrates into “boils” and other cutaneous infections. The monumental work of Brotzu was later expanded at his request by researchers at Oxford with the discovery of cephalosporin C, the structural nucleus for cephalosporin compound development over the next four decades. With continued research and development, several cephalosporin antibiotics have been released since the 1960s, with 24 unique yet structurally similar compounds currently available for clinical use in the United States. The first three generations of cephalosporin antibiotics include both parenterally administered and po-administered agents. The fourth-generation compound, cefepidime, is available for parenteral administration (Table 1).