The gastrointestinal tract is one of the primary lines of defense for the body against pathogens. In a state of health, the gut is able to respond to a pathogen or allergen through various mechanisms. The gut microbiota enhance these defense mechanisms, improve intestinal immunity, aid in nutrient and drug metabolism, and synthesize some nutrients [1]. A disturbance in any of the finely tuned mechanical and immunological components of the intestinal tract, or the microbiota, is likely to disrupt these functions [2]. Prominent causes of gut disruption include inflammation, infection, chemotherapy, radiation, parental nutrition, pharmaceuticals (e.g., antibiotic administration), various diseases, and environmental exposures. Variations can result from diet, gastric acidity, intestinal motility, overall immune status, and general hygiene [3]. Infants and young children are particularly vulnerable to these disruptions because of their developing immune system, and rapid growth and development phase [4]. This chapter will discuss some of the important factors that affect the gut flora, their possible impact on health outcomes, and the remaining gaps in 304our knowledge. Environmental enteropathy (EE), as one of the most prominent conditions affecting the gut flora and function, will be addressed in some detail. This chapter will describe the epidemiology and pathophysiology of EE, its health implications, diagnostic methods, and trials for treatment. Promising avenues for new diagnostic tools and interventions will be highlighted.