Cereals have been one of the major food resources for human diets and animal feed for thousands of years, and a large quantity of by-products is generated throughout the entire processing food chain, from farm to fork. These by-products mostly consist of the germ and outer layers (bran) derived from dry and wet milling of the grains, of the brewers' spent grain generated in the brewing industry, or comprise other types obtained from the breadmaking and starch production industries. Cereal processing by-products are an excellent low-cost source of various compounds such as dietary fibres, proteins, carbohydrates and sugars, minerals and antioxidants (such as polyphenols and vitamins), among others. Often, they are downgraded and end up as waste or, in the best case, are used as animal feed or fertilizers. With the increase in world population coupled with the growing awareness about environmental sustainability and healthy life-styles and well-being, the interest of the industry and the global market to provide novel, sustainable and innovative solutions for the management of cereal-based by-products is also growing rapidly. In that respect, these promising materials can be valorised by applying various biotechnological techniques, thus leading to numerous economic and environmental advantages as well as important opportunities towards new product development (NPD) in the food and feed industry and other types such as chemical, packaging, nutraceutical (dietary supplements and food additives), cosmetic and pharmaceutical industries. This review aims at giving a scientific overview of the potential and the latest advances on the valorisation of cereal-based by-products and wastes. We intended it to be a reference document for scientists, technicians and all those chasing new research topics and opportunities to explore cereal-based by-products through a circular economy approach.