This review covers the role of the sarco(endo)plasmic reticulum in regulating Ca2+influx across the plasma membrane, the role of cytosolic free Ca2+in modulating mitochondrial function, and the role of the plasma membrane in regulating sarco(endo)plasmic reticulum Ca2+, focusing on recent findings that shed a new light on cellular Ca2+regulation. Mechanisms of interactions among the sarco(endo)plasmic reticulum, mitochondria, and the plasma membrane are discussed with a view to explain the lack of consensus regarding the relationship between the cytosolic free Ca2+and blood pressure, and the enigmatic behavior of the Na+-H+exchanger in blood cells (primarily platelets and lymphocytes) from patients with essential hypertension.