Nerve compression syndromes are a common cause of pain, sensory disturbance, and motor weakness in both the upper and the lower extremities. Although carpal tunnel syndrome is frequently diagnosed and treated surgically with success, other compression syndromes are less common and are often best treated nonsurgically. Understanding the anatomy of the major peripheral nerves with respect to intermuscular septa, fibrous bands, muscle margins, and internervous planes is crucial to understanding how and where peripheral nerve compression can occur. Some conditions, such as anterior interosseous nerve syndrome, respond well to nonoperative treatment; others, such as posterior interosseous nerve syndrome, are better treated by surgical intervention. The authors discuss the anatomic and pathologic causes for compression syndromes, as well as guidelines for treatment and outcomes.