This book deals with mental fatigue, or so-called brain fatigue. In the case of long-lasting, mental fatigue can be a disabling consequence of traumatic brain injury, stroke, infection or inflammation in the CNS. Mental fatigue is characterized by pronounced fatigability even after moderate mental activity. Focused attention and concentration are maintained for only short periods of time. A typical feature is a prolonged, profound recovery period needed to restore mental energy. Affected persons often experience associated symptoms: stress sensitivity, irritability, tearfulness, sound- and light sensitivity and headache. It is important to explore the specific nature of the symptom, as this, together with the associated symptoms, constitute an important cause for impaired capacity to work and also to perform everyday activities. In this publication, it is our aim to make a contribution by presenting our understanding of the symptom, its identification, diagnosis, probable mechanisms of origin and perspectives for treatment. We hope that we have been able to stimulate further investigation into mental fatigue after diseases in the CNS thus leading to future innovation in the field.