Myoclonus is a sudden, rapid, shock-like, involuntary movement that can appear in a variety of diseases. The most common form of myoclonus (positive myoclonus) consists of sudden brief muscle activations that lead to fast, shock-like muscle contractions. A distinct form of myoclonus is negative myoclonus, which consists of a transient pause in activation of contracting muscles, leading to brief loss of muscle tension. Positive and negative myoclonus can coexist in the same patient. The study of myoclonus has been the stimulus for a series of elegant investigations of motor system electrophysiology that led to significant new insights into the relationship between cortical activity and movement. Symptomatic drug treatment is effective in many patients, but even in these cases, the effectiveness is often only partial or limited in time. In non-progressive conditions with isolated myoclonus, such as essential myoclonus, symptomatic drug treatment can provide satisfactory control of symptoms for decades. This chapter draws heavily on the current understanding of the neurobiological abnormalities underlying myoclonus. The emphasis is on experimental and clinical evidence, for specific pathogenetic mechanisms. Clinical aspects of the myoclonic syndromes are also mentioned in the chapter.