Vicious cycle of malnutrition and inflammation is a biggest challenge in terms of human health and mortality in the world. The malnutrition-inflammation-chronic diseases syndrome is known to be a common coexistence and association with human health problems. Malnutrition could be developed either due to under-nutrition or due to over-nutrition. Both of these nutritional statuses are capable of creating inflammation. Malnourished human beings, due to under-nutrition, are highly susceptible to many opportunistic pathogens, particularly by the infectious intestinal pathogens. These infectious agents are also well known to induce inflammatory conditions by invoking immune defense mechanisms, particularly various cytokines. The hallmark of many opportunistic infectious intestinal pathogens, such as rotavirus, Vibrio cholerae, Campylobacter jejuni, Shigella, Salmonella and Eschrechia coli (Enterotoxigenic E. coli and Enteropathogenic E. coli), is diarrhea. Diarrhea caused by these infections takes a greater toll on the life of young children in the third world countries, because they are not only malnourished but also basically deficient in many immune enhancing nutrients. Major manifestations of diarrhea is severe dehydration. Although oral rehydration therapy (ORT) has reduced mortality due to cholera, diarrhea still remains a prolific killer of children. While ORT replenishes fluid loss, it is also capable of creating simultaneously a condition resembling post-ischemic reperfusion injury, mediated by reactive oxygen species (ROS). Additionally, studies with intestinal epithelial cell lines have shown that infection induces host cell response that involves particularly the arachidonic acid cascade and invokes upregulation of cyclooxygenase 2 (COX2) leading to the production of Prostaglandine E2 (PGE2) which is known to induce electrogenic chloride secretion in small intestine, a causal factor for diarrhea. In this chapter an attempt has therefore been made to put together some evidences to implicate the role of inflammation in the pathogenesis of diarrheal diseases in malnutrition. © 2013 by Nova Science Publishers, Inc. All rights reserved.