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Presentation of ulnar nerve entrapment at the wrist varies based on differential anatomy and the site or sites of compression. Therefore, an understanding of the anatomy of the Guyon canal is essential for diagnosis in patients presenting with motor and/or sensory deficits in the hand. The etiologies of ulnar nerve compression include soft-tissue tumors; repetitive or acute trauma; the presence of anomalous muscles and fibrous bands; arthritic, synovial, endocrine, and metabolic conditions; and iatrogenic injury. In addition to a thorough history and physical examination, which includes motor, sensory, and vascular assessments, imaging and electrodiagnostic studies facilitate the diagnosis of ulnar nerve lesions at the wrist. Nonsurgical management is appropriate for a distal compression lesion caused by repetitive activity, but surgical decompression is indicated if symptoms persist or worsen over 2 to 4 months.