Following Sharpless′ visionary characterization of several idealized reactions as click reactions, the materials science and synthetic chemistry communities have pursued numerous routes toward the identification and implementation of these click reactions. Herein, we review the radical-mediated thiol–ene reaction as one such click reaction. This reaction has all the desirable features of a click reaction, being highly efficient, simple to execute with no side products and proceeding rapidly to high yield. Further, the thiol–ene reaction is most frequently photoinitiated, particularly for photopolymerizations resulting in highly uniform polymer networks, promoting unique capabilities related to spatial and temporal control of the click reaction. The reaction mechanism and its implementation in various synthetic methodologies, biofunctionalization, surface and polymer modification, and polymerization are all reviewed.