Fatigue is a common problem in neurological disease and associated with substantial disability.Though there is overlapping symptomatology, it is distinguishable from sleepiness, apathy and depression.Convergent data across neurological conditions suggest dysfunction in the striatal-thalamic-frontal system is important in fatigue.This commonality provides some justification for extrapolating data on treatment efficacy from one condition to another. Treatment of fatigue should begin with consideration of all contributing factors, best achieved through a ‘formulation’ approach.Potential causes of fatigue such as medical comorbidity, medication side effects, depression/anxiety, and substance misuse must first be identified and addressed.Once done, across neurological conditions exercise has the best evidence for treatment.Sensibly planned aerobic exercise is safe and should be encouraged in all patients.Cognitive behavioural therapy has reasonable evidence, but availability is limited.Evidence for pharmacological treatments is weak, but amantadine and modafinil are commonly used.