This chapter examines the pathophysiology, diagnosis, treatment, and prognosis of common causes of coma and low arousal states as well as common mimics. It begins with a review of relevant anatomy and physiology pertinent to normal arousal, highlighting important structural and neurochemical processes that can become deranged in various disorders of arousal. It discusses common etiologies of coma organized into structural and toxic/metabolic causes followed by a review of important physical exam, laboratory, imaging, coma scales, and other useful diagnostic testing. Finally, a suggested algorithmic approach is presented to guide timely diagnosis and treatment incorporating important principles highlighted throughout the chapter.