Antibiotics are life-saving drugs against bacterial infections. However, antibiotic resistance undermines their effectiveness and is a serious threat to modern healthcare. In this chapter, we explore how antibiotic treatment affects bacteria and how they evolve resistance to it. After going back in time to learn about the discovery of antibiotics, we explain the mechanisms by which they fight bacteria and discuss the evolution of antibiotic resistance as a process of natural selection. Bacteria may become resistant by acquiring random mutations that allow them to survive and multiply despite treatment. Alternatively, resistance genes can be carried on plasmids—DNA molecules separate from the chromosome, and we explain their role in antibiotic resistance evolution. We finally discuss how our commensal bacteria become resistant to antibiotics and what that means for us.