The endocannabinoid system (ECS) exerts important modulatory functions in the central nervous system (CNS), particularly the retrograde control of excitatory or inhibitory synapses, which enables this system to participate in the control of important neurobiological processes in healthy conditions. However, this physiological relevance acquires a maximal interest in neuropathological conditions affecting either the function or the structures of specific areas of the brain, conditions that have been associated with important changes in the activity of this modulatory system (e.g. losses of CB1 receptors (CB1R), up-regulation of CB2 receptors (CB2R), generation of endocannabinoids) that are susceptible to pharmacological adaptation. Among the group of brain disorders that have been associated with the endocannabinoid system, a special interest has been concentrated in various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and ischemia. These three disorders will be reviewed here from the perspective of the types of changes experienced by the cannabinoid signalling in humans and cellular or animal models, and from a possible usefulness of certain cannabinoid compounds to alleviate symptoms and/or to delay their progression.