The term “nutraceutical” was originally defined by Stephen L. DeFelice, founder and chairman of the Foundation for Innovation in Medicine (Crawford, NJ, USA, 1989), as a combination of the words “nutrition” and “pharmaceutical”: it refers to nutritional products which have effects that are relevant to health. In contrast to pharmaceuticals, however, they are not synthetic substances or chemical compounds formulated for specific indications. According to the European Nutraceutical Association, nutraceuticals are “naturally derived bioactive compounds that are found in foods, dietary supplements and herbal products, and have health promoting, disease preventing, or medicinal properties.” For centuries, people have turned to natural remedies for the prevention and treatment of a variety of common ailments and diseases; with the advent of modern medicine, natural remedies have taken a back seat, giving way to a blooming chemical industry. More recently, the search for less expensive treatments, and the undesirable aggressive side effects often associated with synthetic molecules, have resulted in a turnabout, making the popularity of nutraceuticals soar. As a consequence, the global nutraceutical market was worth about $151 billion in 2011, and it is estimated it will be worth about $207 billion by 2016, with a projected compound annual growth rate of 6.5 %. Such products may range from isolated nutrients, dietary supplements, and specific diets to genetically engineered foods, herbal products, and processed foods such as cereals, soups, and beverages. Nutraceutical categories include dietary supplements (e.g., vitamins, minerals, coenzyme Q, carnitine, and botanicals such as ginseng and gingko biloba), functional foods (e.g., oats, bran, prebiotics, omega-3, plant sterols, and stanols), and medicinal foods (e.g., transgenic plants, health bars with added medications). The best known physiological benefits or protection against chronic disease include antioxidant activity (resveratrol, flavonoids), reduction of hypercholesterolemia (soluble dietary fibers), cancer prevention (broccoli, fiddleheads), and protection against cardiovascular disease (α-linolenic acid). “Natural” is not synonymous with “safe” however, and a cost-effective and scientifically based framework is needed to evaluate both the safety and the effectiveness of these items. Medical researchers need to merge and integrate information from clinical studies into responsible medical practice, and, on the other hand, industry, professional organizations, academia, and health regulatory agencies need to add specific legal and scientific criteria to the definition and standards for nutraceuticals. For their part, analysts are challenged with the development of suitable separation techniques which are capable of providing the resolution and specificity of detection required. Proper knowledge of the qualitative composition and contents of these natural sources is mandatory information for rational consumption and correlation of beneficial effects to dietary intake. An additional issue related to nutraceuticals is that the composition and contents of active constituents in natural sources may vary depending on several factors (climate, season, soil, etc.), and as a consequence it is critical to assess uniform quality, quantification, and standardization. The use of advanced analytical techniques is, therefore, mandatory in all the steps involved in nutraceutical research, from the identification and characterization of new molecules, quantification of their amount in natural sources, and assay of their biological activity to product formulation, quality control, and clinical studies. Given that the complexity of these matrices requires advanced separation/ Published in the topical collection Nutraceuticals and Separations with guest editor Luigi Mondello.