This chapter traces how the modern antibiotic era began with the discoveries of penicillin by Fleming in 1928 and sulfonamides by Domagk in 1932. It lists different classes of antibacterial agents that have been developed for the use in humans. It also describes the various antibacterial agents, including their mechanisms of action, clinical indications, and mechanisms of bacterial resistance. The chapter looks at the core structure of the penicillins, which consists of a thiazolidine ring attached to a β‎-lactam ring and an R-group side chain. It explains how the thiazolidine-β‎-lactam ring provides antibacterial activity while the side chain determines the antimicrobial spectrum and pharmacologic characteristics.