Pesticides are used to control pests before they harm us or our crops. They are selective toxicants in the form and manner used. Pesticides must be effective without human or crop injury. They must also be safe relative to human and environmental toxicology. The study of how the pesticide works on the pest is referred to here as pest toxicology. About 700 pesticides, including insecticides, herbicides, and fungicides, act on perhaps 95 biochemical targets in pest insects, weeds, and destructive fungi. Current insecticides act primarily on four nerve targets, i.e., acetylcholinesterase, the voltage-gated chloride channel, the acetylcholine receptor, and the gamma-aminobutyric acid receptor, systems which are present in animals but not plants. Herbicides act mostly on plant specific pathways by blocking photosynthesis, carotenoid synthesis, or aromatic and branched chain amino acid synthesis essential in plants but not mammals. Many fungicides block ergosterol (the fungal sterol) or tubulin biosynthesis or cytochrome c reductase, while others disrupt basic cellular functions. A major limiting factor in the continuing use of almost all pesticides is the selection of strains not only resistant to the selecting or pressuring compounds but also cross-resistant to other pesticides acting at the same target. One approach to reinstating control is to shift from compounds with the resistant target site or mode of action to another set which have a sensitive target. This type of pesticide management led to the formation of Resistance Action Committees for insecticides, herbicides, and fungicides with very knowledgable experts to define resistance groups, which are in fact listings of primary target sites in pest toxicology. Continued success in pest and pesticide management requires an understanding of comparative biochemistry and molecular toxicology considering pests, people, and crops. Defining and applying the principles of pest toxicology are critical to food production and human health.