Solubilization of lignin and its subsequent valorization are the new frontier for chemicals and products from renewables. Lignin valorization enables favorable economics for a biorefinery, but the efficacy of an organic solvent must be paired with a set of economic and process-based considerations. We describe a methodology for selecting organic solvents for biomass treatment with a specific focus on lignin value prior to pulping (LVPP), a next-generation pulping system. For treatments that do not fiberize or solubilize biomass, we describe elimination and selection criteria that provide a directed search and validation of viable organic solvents. We highlight the economic drivers behind the environmental, process, thermodynamic, and efficacy criteria.