Solvents often constitute the largest material input and a major source of hazard, emissions, energy demand, and waste in chemical manufacture. This chapter examines the environmental and process implications of solvent choice and surveys the principal strategies for replacing conventional hazardous media. It reviews solvent-selection guides and hazard criteria, then considers water, alcohols and esters, bio-based solvents, 2-methyltetrahydrofuran and related ethers, supercritical carbon dioxide, ionic liquids, deep eutectic solvents, and solvent-free or mechanochemical approaches. Emphasis is placed on the fact that a solvent is not intrinsically green: performance must be judged across toxicity, persistence, flammability, renewability, recovery, energy demand, and life-cycle burden. The chapter therefore links solvent substitution with E-Factor and PMI reduction, process intensification, recycling, and safer-by-design decision making. The resulting framework supports solvent selection as a central intervention for improving both chemical-process efficiency and environmental performance.