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T editorial highlights key research challenges associated with closing the loop on the biomass-based biorefinery, with a particular focus on areas in which ACS Sustainable Chemistry & Engineering welcomes manuscripts. While there are established biomass processing industries that are fully entrenched in world economies, most only participate in specific parts along the arc. For example, the pulp and paper industry makes use of lignocellulosic biomassmainly woodto manufacture paper and specialty chemicals, while residual lignin and hemicelluloses (in the form of concentrated spent process liquor) are combusted, resulting in a low-valueadded process with a small product portfolio. Food processors, who work on thin profit margins, are focused on a specific edible portfolio and generally do not manage generated food byproducts and waste streams, nor do they participate in soil regeneration activities. Biorefineries centered around fuel and specialty chemical production are nascent, struggling to become economically viable, and are at this point focused primarily on high-value, low-volume products. The profitable long-term implementation of biorefineries relies on the development of cascade processes able to valorize the rich diversity of biomolecules and building blocks in biomass, targeting a diverse product portfolio (from high-value specialty bioactive compounds and multifunctional materials to platform chemicals and energy). Despite the research and industrial investments into biomass-based processes, there remains a dearth of operations that make use of biomass contributing to a circular economy. Thus far, much of the research efforts have been concentrated on developing processes from food processing byproducts or from novel feedstock sources but have not examined the processes developed in the context of a circular economy. Heterogeneous sources of food waste have been identified and quantified but are not integrated within downstream operations or processes, and financial success hinges upon a diverse product portfolio. This is exacerbated by the absence of uniform metrics to connect extraction processes with other processes or markets. Moreover, because of the nascent nature of the circular biorefinery, applications for chemicals and products are not yet defined, making the required levels of purity uncertain. The term “biomass processing industry” relates to any industry that relies upon biological plant material originating from either marine or terrestrial environments. Scalable processessuch as extraction, fractionation, and separationthat link upstream with downstream operations ostensibly connecting all aspects of biomass production, transformation, distribution, consumption, and disposal are needed to push biomass processing industries into a more sustainable circuit. The connection between upstream and downstream operations must evolve and be realized while being mindful of both economic viability and environmental ramifications. We should look to the adoption of a “no carbon left behind” type of mindset and start more fully integrating both the feedstocks entering into the bioprocessing facility (i.e., increased co-mingling of carbon-rich material, such as mixing existing plastics with biobased monomers) and the waste-tofeedstock distribution (i.e., an industrial ecology approach). Figure 1 shows an idealized biomass processing concept. The