Antimicrobial pharmacotherapy is a broad topic incorporating knowledge of microbiology, pharmacology, and medicine. This chapter provides applied pharmacology knowledge with clinical practice pearls. Evidence-based practice guidelines from the Infectious Diseases Society of America can help direct appropriate therapy. The pharmacodynamics and pharmacokinetics of any antimicrobial agent determine drug efficacy at the site of the infection. The different ways to categorize antimicrobial medications are by class, indication, or mechanism of action. The chapter employs the latter organization as it allows readers to logically categorize drugs, understand side effects, spectrum of activity, and more easily recall the mechanism of action. Each section begins with the prototypical agent and expands upon the class as new drugs were approved that broaden the spectrum of activity, as well as decrease unwanted adverse effects. The chapter helps the reader to define the importance of antibiotic stewardship, and describe the activity of antivirals and antifungal agents.