This provocative commentary critically examines historic definitions for adult malnutrition syndromes as they apply to developed countries with modern healthcare. To stimulate further discussion, the authors propose an updated approach that incorporates current understanding of the systemic inflammatory response to help guide assessment, diagnosis, and treatment. An appreciation of a continuum of inflammatory response in relation to malnutrition syndromes is described. This discussion serves to highlight a research agenda to address deficiencies in diagnostics, biomarkers, and therapeutics of inflammation in relation to malnutrition.