The treatment of individuals with prolonged disorders of consciousness following trauma or other insults to the brain remains a challenge. This chapter reviews definitions of low arousal states, the neurophysiology of consciousness, the pathophysiology of alterations of consciousness, and the basic underlying neurotransmitter functions that may be impacted by injury. Recovery from traumatic and nontraumatic brain injury is characterized by gradual emergence from coma. Depending upon the severity of underlying brain damage, patients may transition from coma to vegetative state to minimally conscious state (MCS) to severe disability, and ultimately to good recovery. Consciousness is a state of awareness dependent upon adequate arousal mechanisms, functioning selective attention, and the ability to perceive and interpret sensory information from the world around us. Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have identified different activation patterns in the brains of patients in vegetative state and MCS. Intracranial complications can impede recovery. Endocrine dysfunction is also associated with traumatic brain injury.