Genetic storage diseases with prominent myoclonus include classic infantile Tay-Sachs disease and juvenile neuropathic Gaucher's disease among the sphingolipidoses, most of the variants of the sialidoses and ceroid-lipofuscinoses, and Lafora disease. The character of the myoclonus differs from disease to disease and often changes as the disease runs its course. For example, massive myoclonic jerks to sound with rapid habituation and a prolonged refractory period are characteristic of the early stages of Tay-Sachs disease; children with late infantile ceroid-lipofuscinosis are most sensitive to light flashes below 3 Hz, those with juvenile Gaucher's disease at 6 to 10 Hz, and those with Lafora disease at 15 to 20 Hz, whereas young adults with sialidosis are not sensitive to either light or sound but are highly sensitive to somatosensory stimulation and movement. Some patients with sialidosis were found to have two distinct types of myoclonus: (a) a stimulus-insensitive facial myoclonus without EEG correlate that persisted in slow-wave sleep and (b) stimulus-sensitive massive jerks associated with vertex positive EEG spikes on which sleep had the paradoxic effect of suppressing jerks while stimulating spikes. Systematic EEG and event-related potential studies, including backward averaging from jerks and detailed anatomic studies of postmortem specimens with modern histochemical techniques, may help illuminate these intriguing differences. New modalities are needed to treat the myoclonus of these diseases since it generally responds poorly to currently available pharmacologic agents.