Cannabinoid receptors can be activated not only by cannabis-derived and synthetic agonists but also by endogenous cannabinoids produced in mammalian tissues and usually referred to as endocannabinoids. There are numerous data in the literature that provide strong support for the notion that the endocannabinoid system (ECS) plays a crucial role in the modulation of several other systems ranging from the central and autonomic nervous systems to the endocrine system, the gastrointestinal tract and the reproductive, immune and cardiovascular systems. The ECS has been reported to become upregulated in a wide range of disorders, such as multiple sclerosis, cancer, schizophrenia, post-traumatic stress disorders, certain types of pain, some intestinal and cardiovascular diseases, excitotoxicity and traumatic head injury. The ECS has prompted a number of important advances in the field of cannabinoid research. It is a key player in several physiological processes and pathological conditions in both central and peripheral tissues.