Understanding the regulation of fat synthesis and the consequences of its misregulation is of profound significance for managing the obesity epidemic and developing obesity therapeutics. Recent work in the roundworm Caenorhabditis elegans has revealed the importance of evolutionarily conserved pathways of fat synthesis and nutrient sensing in adiposity regulation. The powerful combination of mutational and reverse genetic analysis, genomics, lipid analysis, and cell-specific expression studies enables dissection of complicated pathways at the level of a whole organism. This review summarizes recent studies in C. elegans that offer insights into the regulation of adiposity by conserved transcription factors, insulin and growth factor signaling, and unsaturated fatty acid synthesis. Increased understanding of fat-storage pathways might lead to future obesity therapies.