Pain in the hand and wrist can occur with many conditions, including traumatic injuries, inflammatory conditions, nerve-related diagnoses, and various forms of arthropathy. Most of these conditions can improve over time with a combination of pharmacologic, non-surgical therapy, and surgical intervention. Additionally, there are some conditions that require urgent recognition and intervention to avoid significant morbidity and mortality. This chapter reviews common causes of hand and wrist pain, describes the pathophysiology of these conditions, and illuminates the diagnosis and common treatments for each.