Protein modification with the small ubiquitin-related modifier (SUMO) can affect protein function, enzyme activity, protein-protein interactions, protein stability, protein targeting and cellular localization. SUMO influences the function and/or regulation of metabolic enzymes within pathways, and in some cases targets entire metabolic pathways by affecting the activity of transcription factors or by facilitating the translocation of entire metabolic pathways to subcellular compartments. SUMO modification is also a key component of nutrient- and metabolic-sensing mechanisms that regulate cellular metabolism. In addition to its established roles in maintaining metabolic homeostasis, there is increasing evidence that SUMO is a key factor in facilitating cellular stress responses through the regulation and/or adaptation of the most fundamental metabolic processes, including energy and nucleotide metabolism. This review focuses on the role of SUMO in cellular metabolism and metabolic disease.