In recent years, there has been a growing interest in the use of probiotic bacteria for the maintenance of general gastrointestinal health and the prevention or treatment of intestinal infections. Whilst probiotics are documented to reduce or prevent specific infectious diseases of the GI tract, the mechanistic basis of this effect remains unclear. It is likely that diverse modes-of-action contribute to inhibition of pathogens in the gut environment and proposed mechanisms include (i) direct antimicrobial activity through production of bacteriocins or inhibitors of virulence gene expression; (ii) competitive exclusion by competition for binding sites or stimulation of epithelial barrier function; (iii) stimulation of immune responses via increases of sIgA and anti-inflammatory cytokines and regulation of proinflammatory cytokines; and (iv) inhibition of virulence gene or protein expression in gastrointestinal pathogens. In this review, we discuss the modes of action by which probiotic bacteria may reduce gastrointestinal infections, and highlight some recent research which demonstrates the mechanistic basis of probiotic cause and effect.