Post-translational protein modifications by ubiquitin, SUMO and other ubiquitin-like modifiers is common and essential for all eukaryotic organisms. Ubiquitin, SUMO and other ubiquitin-like modifiers are attached to target proteins by a set of related but distinct enzymes including activating enzyme, conjugating enzyme, a ligase and in some cases auxiliary proteins. Both ubiquitin and SUMO proteins regulate most physiological processes in cells and often interdependence of the protein modifications can be observed. Discoveries of ubiquitin and SUMO function have been predominantly driven by studies in cell systems and by in vitro approaches. Investigations of post-translational modifications in Caenorhabditis elegans promises new avenues in ubiquitin and SUMO research. It enables a whole organism approach to study post-translational modifications in development, stress, ageing and in disease models. The biochemical mechanisms of ubiquitin and SUMO modifications are essentially conserved in C. elegans and have been described elsewhere. Thus, this review focuses on emerging research areas where research in C. elegans is advantageous and strongly advances the field of post-translational modifications by ubiquitin and SUMO.