Liquid water can become metastable with respect to its vapor in hydrophobic confinement. The resulting dewetting transitions are often impeded by large kinetic barriers. According to macroscopic theory, such barriers arise from the free energy required to nucleate a critical vapor tube that spans the region between two hydrophobic surfaces-tubes with smaller radii collapse, whereas larger ones grow to dry the entire confined region. Using extensive molecular simulations of water between two nanoscopic hydrophobic surfaces, in conjunction with advanced sampling techniques, here we show that for intersurface separations that thermodynamically favor dewetting, the barrier to dewetting does not correspond to the formation of a (classical) critical vapor tube. Instead, it corresponds to an abrupt transition from an isolated cavity adjacent to one of the confining surfaces to a gap-spanning vapor tube that is already larger than the critical vapor tube anticipated by macroscopic theory. Correspondingly, the barrier to dewetting is also smaller than the classical expectation. We show that the peculiar nature of water density fluctuations adjacent to extended hydrophobic surfacesnamely, the enhanced likelihood of observing low-density fluctuations relative to Gaussian statistics-facilitates this nonclassical behavior. By stabilizing isolated cavities relative to vapor tubes, enhanced water density fluctuations thus stabilize novel pathways, which circumvent the classical barriers and offer diminished resistance to dewetting. Our results thus suggest a key role for fluctuations in speeding up the kinetics of numerous phenomena ranging from Cassie-Wenzel transitions on superhydrophobic surfaces, to hydrophobically driven biomolecular folding and assembly.capillary evaporation | fluctuations | kinetic barriers | assembly T he favorable interactions between two extended hydrophobic surfaces drive numerous biomolecular and colloidal assemblies (1-5), and have been the subject of several theoretical, computational, and experimental inquiries (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Examples include the association of small proteins to form multimeric protein complexes, of amphiphlic block copolymers, dendrimers, or proteins to form vesicular suprastructures, and of patchy colloidal particles into complex crystalline lattices (23-27). When two such hydrophobic surfaces approach each other, water between them becomes metastable with respect to its vapor at a critical separation, d c , that can be quite large (8,9,(28)(29)(30). For nanometer-sized surfaces at ambient conditions, d c is proportional to the characteristic size of the hydrophobic object, whereas for micron-sized and larger surfaces, d c ⌠1 Όm (29, 30). However, due to the presence of large kinetic barriers separating the metastable wet and the stable dry states, the system persists in the wet state, and a dewetting transition is triggered only at much smaller separations (⌠1 nm) (13,22,28,30).To uncover the mechanism of dewetting, a numbe...