Enteric and diarrheal diseases are a major worldwide cause of death among children under the age of 5. In this age group, diarrhea occurs 2.5 billion times per year [1] and causes 15% of childhood deaths.[2] Diarrheal diseases claim 59 million disability-adjusted life years (DALYs), nearly all from children in low- and middle-income countries.[3] Despite this enormous burden, these numbers fail to capture the full impact of enteric and diarrheal diseases. Early and frequent exposure to intestinal pathogens begins a cycle (Figure 1A) that affects digestion, nutrient absorption, growth, and immunity.[4] Repeated infections, with either overt diarrhea or subclinical enteropathy, produce acute and chronic undernutrition,[5] which leads to more frequent and severe infections.[6] Undernutrition contributes to 53% of childhood deaths [7] and is the leading risk factor for poor health outcomes in childhood;[8] survivors are at risk for developmental deficits in growth, fitness, and cognition that persist into adulthood with devastating consequences.[4] These consequences have a multiplicative effect on calculations of DALYs from diarrheal disease.[9] Open in a separate window Figure 1 The vicious cycle of diarrhea and undernutrition in susceptible children (A) The devastating synergy between enteric infections and undernutrition is influenced by the environment, the human genome, host nutrition, and the human microbiome. Various interventions (red boxes) may inhibit progression to the next step in the cycle, minimizing both acute and chronic morbidities. (B) Employing a spectrum of disease outcome measures would lend greater insight into the pathology underlying enteric and diarrheal diseases, while providing a more complete understanding of interventions targeting basic steps of enteric and diarrheal disease pathogenesis. Adapted with permission from Wiley: Nutrition Reviews,4 copyright 2008. http://www.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1753-4887.