Despite the hyperbole often linked with a popular research field, the scientific rationale for probiotics is sound. The probiotic concept is not new but is undergoing transition as knowledge of the gut microbiota in health and disease becomes translated to the clinic. Operationally, a probiotic represents a mimic of and/or supplement to the normal gut microbiota. Much confusion has arisen among consumers because of media misportrayals of probiotics as all being the same. However, with clarification of the molecular basis of host-microbe interactions, the selection criteria for probiotics and the delineation of their distinct mechanisms of action are improving. Most probiotics are from the genus Lactobacillus or Bifidobacterium; this is likely to change and diversify. Similarly, the development of new therapeutic strategies, such as the development of phagebiotics, psychobiotics, and genetically modified pharmabiotics, is poised to become a therapeutic reality.