It is now established that probiotics are strain-dependent, to further advance the concept of probiotic in the maintenance of health and treatment of dysbiosis, the scope of personalized probiotics need to be defined. Currently, probiotic products are marketed worldwide, with the assumption that probiotics with demonstrated health effects work on all people, irrespective of the genetic (ethnicity), environment (geographical location), dietary habit and life style. The effectiveness of probiotics are determined by 1) interactions with prevailing gastrointestinal (GI) commensal microbes, in promoting the establishment of beneficial microbes and elimination of pathogens, 2) Interaction with the host, in achieving a desirable probiotic effect, 3) Interaction with diet, to survive, proliferate and colonize GI, albeit temporary, and in the production of beneficial bioactive metabolites, such as short-chain-fatty acids (e.g. butyric acid), bile acid derivatives and trimethylamines. The benefits acquired from a probiotic are personal, depending on the health status, dietary habit and prevailing GI microbiota. Personalized probiotics should be established to achieve precision administration of specific probiotic effects for targeted population. Globalization and urbanization of human activities have led to merging of dietary habit, thus effective probiotics should evolve in tandem. Ultimately the probiotics of choice should be directed at specific physiological stage, health condition and targeted diseases.