This work draws attention to both prospects and challenges for silica monoliths in solid-liquid catalysis at ultrahigh efficiency. The fundamental advantages of silica monoliths as support structure over particulate fixed beds and organic-polymer monoliths are illustrated as well as recent applications as flow-through microreactors for the production of fine chemicals. Preparation routes to sol-gel and porous glass-based silica monoliths featuring a hierarchical pore structure are described and their potential use as short-contact-time reactors is highlighted together with a view on the multiscale characterization and their rational design by establishing quantitative synthesis-morphology-transport relationships.