Lysosomal storage diseases are characterized by enzyme deficiency in the lysosomal appar-atus of the cell, triggering a pathological accumulation of undigested cellular material (proteins, lipids or carbohydrates) and tissue damage. Clinically and etiologically dive-rse, this group includes over 70 presently recognized hereditary conditions with no known effective therapy. Thus, the search for therapeutic strategies directed at these disorders represents an urgent unmet biomedical task, also necessitating the use of appropriate and valid experimental (animal) models. Here, we discuss the existing models of lysosomal storage diseases and the applicability of rodent and zebrafish as model organisms for probing these diseases.