Osteoarthritis (OA) is common in the elderly, but also affects younger people. The disease symptoms are debilitating and, as well as causing physical impairment, can affect the psychosocial wellbeing of the patient. Furthermore, the impact of this disease is substantially increased by the common occurrence of comorbid conditions, such as hypertension and renal impairment. Non-steroidal anti-inflammatory drugs are commonly used to treat the symptoms of OA, but their related gastrointestinal side-effects increase the impact of this disease. Gastrointestinal tolerability should therefore be considered in the design of new therapies that reduce the symptoms and activity of OA. Furthermore, because this disease is associated with comorbid conditions, patient safety must also be considered when designing new therapies.