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The discovery of antibiotics less than 80 years ago played a major role in increasing life expectancy throughout the world. Prior to 1918, the average life expectancy in the United States was 45 to 50 years. Life expectancy is now between 70 and 75 years, thanks in part to antibiotics. Yet we face the possibility that antibiotics will become useless. Over several decades, indiscriminate use of antibiotics has fueled a rise in antibiotic resistant bacterial strains. Humans are now vulnerable to infectious diseases once considered conquered. This chapter addresses important questions about chemotherapeutic agents including: Why do antimicrobials inhibit the growth of bacteria, but not humans or animals? How do microbes develop antibiotic resistance? How do clinicians know which antibiotic to use to treat an infection? We will also discuss what makes a good antibiotic target, and how new antibiotics are discovered.