Fasting has been practiced for millennia, for religious, ethical, or health reasons. It is also commonplace among different species, from humans, to animals, to lower eukaryotes. Research on fasting is gaining traction based on recent studies that show its role in many adaptive cellular responses such as the reduction of oxidative damage and inflammation, increase of energy metabolism, and in boosting cellular protection. In this expert review, we recount the historical evolution of fasting and we critically analyze its current medical applications, including benefits and caveats. Based on the available data, we conclude that the manipulation of dietary intake, in the form of calorie restriction, intermittent fasting, dietary restriction with the exclusion of some nutrients, prolonged fasting, and so forth, is anthropologically engraved in human culture possibly because of its positive health effects. Indeed, many studies show that fasting ameliorates many biochemical parameters related to cardiovascular and cancer risk, and neurodegeneration. Mechanistic studies are plentiful, but largely limited to cell cultures or laboratory animals. Understandably, there are no controlled trials of any form of fasting that gauge the effects on [any cause] mortality. Physicians should be aware that misinformation is pervasive and that their patients often adopt dietary regimens that are far from being clinically validated. Moreover, doctors are often unaware of their patients' religious or traditional fasting and of its potential health effects. Based on current evidence, no long-term fasting should be undertaken without medical supervision until future research will hopefully help shed further light on fasting and its effects on human health.