Cumulative evidence reveals that diabetes is a condition in which cell Ca2+ homeostasis is impaired. Defects in cell Ca2+ regulation were found in erythrocytes, cardiac muscle, platelets, skeletal muscle, kidney, aorta, adipocytes, liver, osteoblasts, arteries, lens, peripheral nerves, brain synaptosomes, retinal tissue, and pancreatic beta cells, confirming that this defect in cell Ca2+ metabolism is a basic pathology associated with the diabetic state. Though different defects in a variety of functions that regulate cell Ca2+ homeostasis were described in diabetes, the most common finding is an increase in [Ca2+]i levels. However, it is not clear whether the defect in cell Ca2+ metabolism in diabetes precedes or succeeds the overt diabetic condition. It is also not clear which of the multiple functions involved in cell Ca2+ regulation has the primary defect. Defects in cell Ca2+ metabolism may be significant for the observed pathologies in insulin secretion and insulin action in diabetes. They may also play an important role in the vascular complications seen in this condition, such as hypertension, atherosclerosis, and microangiopathy. Therefore, better understanding of the impairment in cell Ca2+ metabolism in diabetes may markedly enhance our understanding of this condition.