The nematode Caenorhabditis elegans is the simplest animal model available to study human disease. In this review, the worm homologues for the 58 human genes involved in lysosomal storage disorders and for 105 human genes associated with lysosomal function have been compiled. Most human genes had at least one worm homologue. In addition, the phenotypes of 147 mutants, in which these genes have been disrupted or knocked down, have been summarized and discussed. The phenotypic spectrum of worm models of lysosomal storage disorders varies from lethality to none obvious, with a large variety of intermediate phenotypes. The genetic power of C. elegans provides a means to identify genes involved in specific processes with relative ease. The overview of potential lysosomal phenotypes presented here might be used as a starting point for the phenotypic characterization of newly developed knock-out models or for the design of genetic screens selecting for loss or gain of suitable knock-out model phenotypes. Screens for genes involved in lysosomal biogenesis and function have been performed successfully resulting in the cup and glo mutants, but screens involving subtle phenotypes are likely to be difficult.