Changes in intracellular Ca²⁺-concentration play an important role in the excitation–contraction–relaxation cycle of skeletal muscle. In this review we describe various inheritable muscle diseases to highlight the role of Ca²⁺ -regulatory mechanisms. Upon excitation the ryanodine receptor releases Ca²⁺ in the cytosol. During and after contraction the sarcoplasmic reticulum (SR) Ca²⁺ ATPase (SERCA) pumps Ca²⁺ back in the SR resulting in relaxation. An abnormal change in the intracellular Ca²⁺ -concentration results in defective muscle contraction and/or relaxation, which is the cause of various muscle diseases. Malignant hyperthermia (MH) and central core disease (CCD) are both caused by mutations in the ryanodine receptor but show different clinical phenotypes. In MH an acute increase of Ca²⁺ results in excessive muscle contraction causing rigidity, while in CCD a chronic rise of cytosolic Ca²⁺ is seen, leading to mitochondrial damage, disorganization of myofibrils and muscle weakness. In Brody disease and also in mitochondrial myopathies, SERCA functions sub optimal causing a prolonged physiological Ca²⁺ -elevation leading to slowing of relaxation. Defective actin–myosin interactions, as in nemaline myopathy and also in mitochondrial myopathies due to ATP-shortage, cause Ca²⁺-hyposensitivity and slowness of contraction. Information of Ca²⁺ -kinetics in these inherited muscular diseases improves our understanding of the role of calcium in the physiology and pathophysiology of the skeletal muscle cell.