Liquid‐assisted grinding (LAG) has emerged as a powerful and sustainable strategy in medicinal mechanochemistry, enabling the rapid, selective, and solvent‐minimized synthesis of pharmaceuticals and drug‐like molecules. This review systematically examines the transformative potential of LAG in constructing pharmacologically relevant architectures, highlighting its consistent superiority over both neat grinding and conventional solution‐based approaches, particularly in enhancing reactivity and exerting precise control over chemo‐, regio‐, stereo‐ and enantioselectivity. Central to this discussion is the multifaceted role of the liquid additives, which function not merely as processing aids but as dynamic mediators that modulate the microenvironment, acting as ligands or cocatalysts, functional reagents, and stabilizers to direct selectivity. The review concludes by addressing current challenges and outlining strategic pathways to advance LAG toward scalable, greener, and industrially viable pharmaceutical synthesis.
Fang et al. (Tue,) studied this question.