Microbes make up a significant component of the human body, yet relatively little is known about how they influence health and disease. They colonize after birth by chance and circumstance, yet play a major role in immunity, digestion, and protection against disease. In relatively recent times, basic science and clinical studies have clearly shown the potential impact of indigenous and exogenous microbes on human health and well-being. Yet regulatory bodies, research funding agencies, and health care practitioners, perhaps disillusioned by too many unreliable, overhyped products that are marketed under the guise of probiotics or natural therapeutics, have lagged far behind in embracing this avenue of enquiry. As more scientifically proven probiotic products differentiate themselves from untested and unproven cure-alls, and as multidisciplinary research groups piece together the diverse components of the puzzle, humans will slowly begin to understand how best to optimize their coexistence with microbial organisms, thus perhaps prolonging and enhancing life.