The most common types of calcium-containing crystals that are associated with joint and periarticular disorders are calcium pyrophosphate dihydrate (CPP) and basic calcium phosphate (BCP) crystals. Several diverse but difficult-to-treat acute and chronic arthropathies and other clinical syndromes are associated with the deposition of these crystals. Although the pathogenic mechanism of calcium crystal deposition is partially understood, much remains to be investigated, as no drug is available to prevent crystal deposition, permit crystal dissolution or specifically target the pathogenic effects that result in the clinical manifestations. In this Review, the main clinical manifestations of CPP and BCP crystal deposition are discussed, along with the biological effects of these crystals, current therapeutic approaches and future directions in therapy.