This chapter focuses on brain and spinal cord trauma, as well as nontraumatic spinal cord diseases, including vascular, infectious, and hereditary etiologies. Traumatic brain and spinal cord injuries are among the most critical and time-sensitive emergencies encountered in neurology. Rapid recognition of critical presentations such as increased intracranial pressure, brain herniation syndromes, and neurogenic shock is essential to any neurologist and greatly affects the prognosis of the patient. We will review mechanisms of injury, common clinical presentations and imaging findings, diagnostic strategies, and acute management of these conditions. In addition, we will review a spectrum of nontraumatic spinal cord diseases, some of which also require timely recognition and management, such as spinal cord infarct and cauda equina syndrome. Other nontraumatic spinal cord conditions such as infectious myelitis and hereditary myelopathies will also be discussed. While there are innumerous conditions that can affect the spinal cord, knowledge of the clinical presentations and the predilections of disease processes to different anatomical locations of the spinal cord will help you tailor your investigation and arrive at the correct diagnosis.