Innate immunity is an evolutionary ancient defence strategy that serves to eliminate infectious 19 agents while maintaining host health. It involves a complex network of sensors, signaling proteins 20 and immune effectors that detect the danger, then relay and execute the immune programme. Post-21 translational modifications relying on conserved ubiquitin and ubiquitin-like proteins are an integral 22 part of the system. Studies using invertebrate models of infection, such as the nematode 23 Caenorhabditis elegans, have greatly contributed to our understanding of how ubiquitin-related 24 processes act in immune sensing, regulate immune signaling pathways, and participate to host 25 defence responses. This review highlights the interest of working with a genetically tractable model 26 organism and illustrates how C. elegans has been used to identify ubiquitin-dependent immune 27 mechanisms, discover novel ubiquitin-based resistance strategies that mediate pathogen clearance, 28and unravel the role of ubiquitin-related processes in tolerance, preserving host fitness during 29 pathogen attack. Special emphasis is placed on processes that are conserved in mammals.