Muscle channelopathies are inherited disorders that cause paralysis and myotonia. Molecular technology has contributed immeasurably to diagnostic testing, to correlation of genotype with phenotype, and to insight into the pathophysiology of these disorders. In most cases, the diagnosis of muscle channelopathy is still made on clinical grounds, but is supported by ancillary laboratory and electrodiagnostic testing such as serum potassium measurement, exercise testing, repetitive nerve stimulation, needle electromyography, calculation of muscle fiber conduction velocity, or electromyography power spectra. Although provocative glucose or potassium challenges are now infrequently performed, they have contributed greatly to our understanding of the pathophysiology of these disorders, and to our ability to differentiate between periodic paralysis types. Despite considerable progress, ample opportunity remains for future clinical research, particularly in expanding genotype-phenotype correlations and in optimizing electrodiagnostic methods. With respect to diagnostic testing, there is a need for accurate, efficient, and cost-effective bedside testing, given the substantial proportion (as high as 20%) of genetically undefined cases. Even in genetically defined cases, minimal clinical expressivity due to incomplete penetrance poses a significant challenge to currently available nonmolecular testing.