Calcium plays a vital role in maintaining homeostasis and has functions in various bodily processes. This chapter explains the different fractions of calcium in the body and the key components of calcium homeostasis. It provides an overview of diagnostic tests for investigating calcium disorders and describes the clinical signs, causes and mechanisms of hypercalcemia and hypocalcemia. Specific diseases associated with these conditions, such as primary hyperparathyroidism, kidney disease, neoplasia and nutritional deficiencies, are also covered. The clinical features and signalment of affected animals are discussed, as well as the management and treatment of these conditions.