The discovery of cephalosporin C and its conversion to 7-aminocephalosporanic acid (7-ACA) are reviewed. The syntheses of cefamandole and three other injectable cephalosporins from 7-ACA are described, and the antibiotic properties of the four drugs are compared. The microbiological potency of cefamandole is comparable to that of cephalothin, cephaloridine, and cefazolin against gram-positive organisms. Cefamandole is the most potent of the four compounds against gram-negative bacteria. In addition, cefamandole inhibits Enterobacter and strains of indole-positive Proteus which have been traditionally resistant to the cephalosporins. For pharmaceutical reasons cefamandole nafate was chosen for the clinical formulation of the antibiotic.