The potential utility of drugs modulating the endogenous cannabinoid signaling system is reviewed in the present work. The discovery in 1988 of a brain cannabinoid receptor (CB1) and the isolation in 1992 of the first endogenous ligand for that receptor, anandamide, demonstrated the existence in the brain of an endogenous cannabinoid signaling system. The recent development of new drugs such as those aimed to interact with either the CB₁ or the mechanisms involved on the release, uptake and degradation of endogenous cannabinoids will help to develop new strategies for the treatment of psychiatric and neurological disorders. They include the psychosis, addiction, motor disorders such as Parkinson`s disease and choreas, epilepsy, pain, appetite and memory. The old social claim of using marijuana as a medicine has now become a very active scientific field of research thanks to the recent advances in the neuropharmacology of the endogenous cannabinoid system.