Proteolytic enzymes (proteases) comprise a family of enzymes which hydrolyse protein or peptide substrates in the generalised process of intracellular protein degradation, a process essential for the normal functioning of all cells. Proteases may also have a wide range of additional functions, including metabolic control of physiologically active oligopeptides or precursor protein forms, antigen presentation/recognition by the major histocompatibility complex in the cellular immune response, as well as in digestion, blood clotting, complement activation, etc. In this article, the nomenclature and classification of proteolytic enzymes in skeletal muscle, and their role in normal muscle physiological processes have been reviewed, including exercise, muscle development and ageing. Although proteases play an important role in normal muscle functioning, in pathological situations the enzymes may themselves be regarded as 'toxic agents' in terms of their damaging effects on muscle tissue. Muscle damage resulting from inappropriate activity of proteolytic enzymes in muscle wasting associated with muscular dystrophies, denervation atrophy, inflammatory myopathies, cancer, sepsis, diabetes and alcoholism have been reviewed. In addition, evidence that the adverse effects of drugs known to induce muscle wasting, such as corticosteroids, (or beneficial effects of growth promoting drugs) may be mediated via proteolytic enzymes is also reviewed.