Osteoarthritis (OA) is the most common joint condition globally, affecting 10% of men and 18% of women over the age of 60. Its pathogenesis is multifactorial, which has made identifying modifiable factors to slow the progression or prevent the development of OA challenging. Current treatment focuses largely on lifestyle modification, analgesia and ultimately joint replacement, with no specific therapies currently available. However, research is on-going to provide a disease-modifying drug akin to those available for rheumatoid arthritis. The heterogeneity of OA has allowed a variety of pharmaceutical agents to be considered, each aiming to modify different components of the arthritic joint. Only a limited number of targeted treatments have been found to be efficacious, and those that have been identified have been associated with adverse events, preventing their progression to clinical practice. This article reviews the current management of OA, including tissue-specific approaches and treatments and summarizes the on-going research that aims to identify further therapeutic targets and develop disease-modifying OA drugs.