Cysteine proteases belong to C1 family, which includes plant and lysosomal cathepsin-like proteases. Cathepsins, detected and isolated from numerous biological sources, are well adapted to acidic and reducing conditions of lysosomal system. Cathepsins perform the activities of a wide variety of enzymes such as broad- and narrow-range endo-peptidases, aminopeptidases, dipeptidyl peptidases with exo- and endopeptidases. They are involved in many physiological events. The enzymes can be destructive if their activity is not controlled by their endogenous inhibitors. Eleven cathepsins, i.e., B, C, F, H, K, L, O, S, V, W, and X or Z, designated so far in human are also identified in other organisms. Although there are great deal of information available on the physiological function of these cathepsins at cellular level very little is known about their function at organism level. The genome sequences from many organisms including human, Drosophila, and free-living nematode, Caenorhabditis elegans allow comparative genomics as the first order functional analysis. The genome sequence of C. elegans allows comparative sequence analyses to identify parasite or human gene that share homology with C. elegans. Genome sequences in combination with an ideal model system such as C. elegans will facilitate identification of key cellular functions that could lead to the identification of mechanisms of drug resistance, as well as discovery of novel drug targets and antigens with vaccine potential. This review covers recent research on the role of "papain-like" class of cysteine proteases in cellular physiology and focuses on most comprehensively studied cathepsin B and L enzymes in C. elegans. Besides, it also reviews the function of a recently described cathepsin Z.