Osteoarthritis is the leading musculoskeletal cause of disability in western society. Despite this, it is still difficult to gain a precise definition of what osteoarthritis actually is. It is well known that there is a modest correlation between x-ray changes and pain. However, for knee joint structure there is largely consistent evidence that bone marrow lesions, synovitis/effusions and cartilage defects are associated with knee pain and cartilage loss. In addition, muscle strength and obesity predict pain even in the absence of structural knee pathology. Finally, the pain system itself is involved with both pain processing and genetic factors implicated in recent studies. These improvements in basic science have greatly enhanced our understanding that osteoarthritis is an umbrella term for a number of pathways leading to very similar pain and structural outcomes; these outcomes are leading to lesion-specific therapies, which indicate the importance of trying to pinpoint causes of pain in the individual.