Phytoalexins are antibiotics that accumulate in plant cells in response to microbial attack. In this role they are a critical part of resistance to most potential pathogens that attack the plant. In cotton various terpenoids derived from cadalene act as phytoalexins. Other constitutive terpenes, such as gossypol, heliocides, and caryophyllene, are derived from the same biochemical precursors as the phytoalexins and accumulate in pigment glands and root bark of healthy plants as protectants against herbivores. In this brief review we have summarized methods for studying the cotton phytoalexins and recent attempts to use conventional and molecular genetics to manipulate these compounds for better resistance to diseases and pests.