Degenerative arthritis is a prevalent joint disorder marked by progressive cartilage breakdown, subchondral bone remodeling, and the formation of osteophytes. This pathology can lead to significant functional impairment. Early recognition and targeted interventions are essential for effectively managing this disease. This chapter presents an in-depth exploration of the epidemiology, clinical presentation, and diagnostic evaluation of hand and wrist osteoarthritis. It focuses on the intricate relationship between inflammatory pathways and biomechanical forces that contribute to the progression of this debilitating condition. Current treatment strategies encompass a broad spectrum, ranging from conservative approaches such as splinting and tailored physical therapy to the use of pharmacologic interventions that aim to alleviate pain and improve function. Additionally, surgical options, including various forms of arthroplasty, arthrodesis, and minimally invasive techniques, provide pathways to restore mobility and improve the quality of life for individuals affected by these conditions. Emerging regenerative therapies, particularly innovations in stem cell applications and biologics, present promising opportunities not only for halting the trajectory of degenerative changes but also for potentially reversing them. By examining the multifaceted risk factors, underlying pathophysiological mechanisms, and the latest advancements in treatment together, this chapter underscores the pivotal role of biomechanics in optimizing patient outcomes. It also aims to inform and shape actual management strategies for degenerative arthritis affecting the hand and wrist, ensuring a comprehensive approach to this widespread health concern.