Knowledge of the fundamental aspects of the pathophysiology of compartment syndrome and the variations that are encountered in differing etiologic events is crucial to make cogent decisions when caring for the patient involved whether this be head trauma with brain injury, glaucoma, or extremity trauma problems involving muscular or neural function. Concerning extremity muscle and nerve injury, nerves will function for 70 minutes after ischemia reaches a critical point. Paralysis will then occur and the involved limb will become painless. Muscle and nerve will tolerate 4-hour ischemia and functionally survive. Six hours of ischemia causes variable injury to muscle and nerve. Eight-hour ischemia yields permanent damage to both nerve and muscle. Varying types of injury (low vs. velocity trauma, high-velocity gunshot or blast injury, temporary vascular interruption, etc) produce different clinical pictures. Understanding the pathophysiology of these is important in planning appropriate early and even prophylactic care of each patient.