There is resurgent interest in the use of probiotics to maintain gastrointestinal and systemic health, driven by recent advances in knowledge of bacterial interactions with the epithelium and innate immune system of the intestine. The effects of probiotic bacteria on the intestinal epithelium and their downstream consequences are reviewed. Probiotics prevent pathogen adherence and invasion of the epithelium, partly by blocking adherence sites but also by upregulating gene expression of MUC2 and of antimicrobial peptides. Metabolic effects of probiotics on the intestinal epithelium include production of short chain fatty acids which influence epithelial cell metabolism, turnover and apoptosis. Bacterial metabolism of unabsorbed dietary constituents with production of free radicals and phenolic metabolites can lead to DNA damage and cancer; probiotics restore eubiosis and potentially prevent this. Probiotics alter expression and redistribution of tight junction proteins and reduce intestinal permeability limiting absorption of noxious molecules from the gut lumen. Most studied are the effects of probiotics on epithelial cells which are the first line of innate immune-capable cells that encounter luminal flora. Probiotics, through secreted molecules, influence the innate inflammatory response of epithelial cells to stimuli from the gut lumen, and reduce mucosal inflammation. Through effects on dendritic, and possibly epithelial, cells they influence naïve T cells in the lamina propria of the gut and thus influence adaptive immunity. These varied effects of probiotics have implications for the treatment of several gastrointestinal diseases including antibiotic-associated colitis, acute gastroenteritis, inflammatory bowel disease, colon cancer, and irritable bowel syndrome.