Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromes—noninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. Inflammatory diarrhea is caused by two groups of organisms—cytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.