Chemotherapy is one of the pillars of cancer treatment, with first reports of its use dating back hundreds of years. Cytotoxic drugs damage malignant cells through various mechanisms, leading to creation of several pharmacologic classes. In this chapter, we first describe the cell cycle and how a cell, whether healthy or cancerous, maintains its genome and replication capability. Then, we discuss the mechanisms by which most cytotoxic medications inhibit cell proliferation. Lastly, we mention the most notable and commonly used cytotoxic chemotherapy drugs available with a short description of each.