For skeletal muscle to contract normally, signals from the neuromuscular junction must be conveyed to the contractile proteins by action potentials that spread across the surface membrane and into the T-tubular system. Hyperexcitability in the surface membrane can lead to unwanted and persistent contraction, while reduced excitability can cause weakness or paralysis. Many of the human muscle diseases that are associated with abnormalities of membrane excitability have been linked to defects in the function of membrane ion channels. Using molecular biologic tools, these abnormal channels can be identified and their molecular defects defined. Advances in these areas now provide the basis for a rational, mechanistic approach to the classification and treatment of these disorders of membrane excitation.