Osteoarthritis is the most common form of arthritis in adults and its incidence increases with age. More than 50% of people aged 65 and older have radiographic changes of knee osteoarthritis. Calcium crystals, including calcium pyrophosphate dihydrate and basic calcium phosphate crystals, are also common in the elderly. Not surprisingly, osteoarthritis and crystal arthropathy frequently coexist. The question of a role for calcium crystals in causing or worsening osteoarthritis has been pondered for many years. Progress in understanding the interrelationships between calcium crystals and osteoarthritis has been slowed by our limited knowledge of the pathogenesis of both osteoarthritis and calcium crystal-induced arthritis and our limited ability to accurately detect calcium crystals. Nonetheless, there are good data from clinical and laboratory studies supporting an important role for calcium crystals in osteoarthritis.