The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potential of ECS in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, Huntington’s disease, Tourette’s syndrome, brain ischemia and amyotrophic lateral sclerosis (ALS). Elements of the ECS, such as fatty acid amide hydrolase or the cannabinoid receptors are now considered as promising pharmacological targets for some diseases. Although still preliminary, recent reports suggest that modulation of the ECS may constitute a novel approach for the treatment of AD. There are windows of opportunity in conditions caused by acute events such as trauma and ischemia as well in conditions that may involve altered functionality of the target receptors of the ECS, such as in AD. The ECS changes in Parkinson’s disease could be compensatory as well as pathogenic of the illness process and needs further understanding and clinical studies are still in the preliminary stage. There is not enough evidence to support use of cannabinoids in treating Huntington’s disease, tics and obsessive compulsive behaviour in Tourette's syndrome. Evidence on therapeutic use of cannabinoids in multiple sclerosis and ALS is currently limited. A major challenge for future research is the development of novel compounds with more selectivity for various components of the ECS which could target different neurotoxic pathways and be used in combination therapy.