Cannabis has been used by humans since ancient history, but it was not until the 1960s, with the isolation of Δ9-tetrahydrocannabinol (Δ9-THC), that research with cannabinoids took off. One of the most important findings was the discovery of the endocannabinoid system; this system is formed by the cannabinoid receptors, endogenous ligands of these receptors, and enzymes and proteins that regulate ligand concentration. Components of the endocannabinoid system can be found in most parts of the organism and have different functions, but primarily it is a system that maintains homeostasis. Apart from the endocannabinoids, exogenous substances can bind to these receptors. These can be cannabinoid agonists found in the Cannabis sativa plant, such as Δ9-THC, which is the substance responsible for the psychoactive effects of cannabis, or synthetic cannabinoids, as of this writing available only for research purposes (but also used as substances of abuse). This chapter mainly focuses on endocannabinoids, as other agonists are explained in other chapters.