Many animals use venoms or toxins to protect themselves against predators or to obtain prey. Thus, there is strong selection pressure to evolve resistance to these toxins on the part of the targeted animal and, in the case of alkaloid toxins that may diffuse throughout the body, in the animal that possess the toxins. I will first describe a situation in which a predator—the grasshopper mouse—has evolved resistance to voltage-gated sodium channel-targeting peptide components in the venom of their scorpion prey. This allows these carnivorous mice to exploit an abundant food resource in the Sonoran Desert in America. Then, I will show how poison arrow frogs from South America have evolved resistance to the acetylcholine receptor agonist epibatidine which is found in different independently evolved lineages of frogs. In both examples, resistance is conferred by a single, or at most a few, amino acid substitutions in key parts of the target molecule.