Publisher Summary This chapter presents that endocannabinoid juxtacrine and paracrine signaling is widespread throughout the brain and body, representing one of the most prevalent lipid/fatty acid-based intercellular communication systems in mammals. The cannabinoid part of the name is derived from the cannabis sativa plant and the drugs, marijuana and hashish among others, made from this plant. It discusses that the receptors for these drugs are the major targets of a group of lipid derived signaling molecules known as the eCBs. Two arachidonoyl-containing fatty acids, arachidonoylethanolamide (AEA or anandamide) and 2-arachydonoyl glycerol (2-AG) are thought to produce the majority of eCB signaling. These two compounds are synthesized from arachidonate-containing membrane lipids via separate pathways consisting of several enzyme-catalyzed steps. The chapter also reviews that the CB1 receptor is the main mediator of eCB actions in the brain, and is responsible for the majority of the intoxicating effects of natural and synthetic cannabinoid drugs. Endocannabinoids can also activate the CB2 receptor that is mainly found in the periphery but is apparently also present in the central nervous system (CNS).