Calcium-containing crystals are the most common class for the osteoarthritic joint. They are responsible for acute periarthritis and destructive arthropathies, and for tissue deposits mimicking tumor-like masses. These crystals encompassed mainly calcium pyrophosphate dihydrate and basic calcium phosphate crystals, with the latter being related to hydroxyapatite, carbonate-substituted apatite, and octacalcium phosphate. Calcification deposit mechanisms will be reviewed with respect to extracellular inorganic pyrophosphate dysregulation mainly caused by modulation of specific membrane channel disorders. Genetic defects have been extensively studied and identified mutation of specific genes such as ANKH and COL. Pathogenesis of crystal-induced inflammation is related to synovial tissue and direct cartilage activation. Besides classical knee or wrist pseudogout attacks or Milwaukee shoulder arthropathies, clinicians should be aware of other specific common presentations, such as erosive calcifications, spinal cord compression by intraspinal masses, ligamentum flavum calcification, or atypical calcified tophus. Promising clinical results for preventing calcium crystal deposits and cartilage degradation are lacking. Practical imaging tools are needed to monitor reduction of calcification of fibrocartilage and articular cartilage as markers of drug efficacy.