A wide variety of different feedstocks and conversion technologies may be used in a biorefinery to produce fuel, chemicals, feed, and power or heat. Biorefineries can also have a wide range of capacities and, given the dependency on technological innovation, funding, and market conditions, it is difficult to predict their future prospects. In this sense, technoeconomic assessment is an essential tool for the designing of an economically viable biorefinery with a long-term perspective, since it provides decision-making information for the corresponding steps of the investment. In this chapter, the technoeconomic considerations of advanced biorefinery concepts are presented and discussed. Focus is given to how technoeconomic assessment influences the design decisions and challenges for establishing novel technologies. The economics of current biomass fractionation methods, fuels, and biochemical production technologies are also presented. Finally, the current trends on improving the economics of biorefineries are discussed, as an attempt to help the reader identify synergies and opportunities for further improvement strategies.