As flow chemistry occurs, reactive extrusion becomes a technique that allows chemical reactions to be completely solvent-free. Eliminating potentially toxic solvents makes the process environmentally friendly. However, it creates many engineering challenges because it requires a comprehensive redesign of existing industrial processes. Although extrusion processes have been widely used and studied by polymer and materials experts, only other chemists are now beginning to investigate their possibilities for preparing organic compounds. Classic extrusion methods involve grinding reagents in a ball mill, but more advanced extrusion techniques using screws can even allow these solvent-free reactions to operate in a flow setting. Once again, the downside is to effectively tune the system and expand them. In their laboratory, chemists use ball mills to prepare several attractive products-amino acids, osmium, nitrones, and peptides-and have already implemented some very classic organic reactions-Suzuki coupling, click chemistry-but Examples under reactive extrusion conditions other than polymers still remain quite elusive. However, rare exceptions show great promise. Biotechnology company Amgen reports optimized eutectic synthesis that can be used to treat chronic pain, and this is also the first example of mechanochemical synthesis, which can be scaled up to hundreds of grams. In addition, British scientists have used reactive extrusion to efficiently prepare deep eutectic solvents-a class of ionic liquids that could become a new generation of green, non-flammable solvents. Both of the previous examples involved the formation of intramolecular interactions, but not the creation of new covalent bonds. However, chemists recently reported the formation of metal-organic frameworks (MOFs) and discrete metal complexes extruded by screws, opening up new possibilities for cleaner, more sustainable solvent-free chemistry.