Consumption of dietary ellagitannins (ETs) has been associated with different health benefits. Nonetheless, ETs are not bioavailable as such and are metabolized in vivo. They are partially converted into ellagic acid (EA) in the upper gastrointestinal (GI) tract, but this first metabolite is also poorly bioavailable. In the lower GI tract, EA and residual ETs are metabolized by gut microbiota to produce urolithins, which, together with their conjugate relatives, persist at relatively high concentrations in plasma and urine for days after ingestion of dietary ETs. Thus, ETs and EA may exert local health benefits on the GI tract but systemic health benefits are more likely to result from urolithins. Cellular models suggest that, at physiological concentration, urolithins are active against chronic degenerative diseases. Health benefits have been proven in animal models and during clinical studies. Even so, the crucial involvement of gut microbiota in ET bioconversion induces important variability of physiological response among humans, giving rise to the concept of high and low urolithin producers. This variability among consumers in obtaining potential health benefits from dietary ETs raises new challenges for the functional food industry. Different research perspectives are discussed to tackle this significant issue for nutritionists, food technologists, and consumers.