Decompression of deep, hot continental crust is the primary mechanism of crustal melting, with major consequences for the geodynamics of orogens. Decompression within thickened continental crust may be initiated by processes driven from above (erosion, tectonic denudation) and/or below (crust/lithosphere thinning, buoyant rise of deep crust). On a larger scale, decompression of subducted continental crust may add material, including melt, to the overlying, non-subducting plate. This mechanism has the potential to produce large amounts of melt because fertile material is continually conveyed into the mantle, where it eventually buoyantly ascends and melts. Decompression-driven melting of continental crust may account for the high melt fractions (≥20 vol.%) and great thickness (20-30 km) inferred for the partially molten layer in orogenic crust. When high melt volumes are present in the crust and/or the thickness of the partially molten layer is large, the subsequent thermo-mechanical evolution of orogens is strongly influenced by lateral (channel) and vertical (buoyant) crustal flow. For both lateral and vertical flow, the presence of melt decouples deep crust from upper crust, and continental crust from mantle lithosphere. A major consequence of vertical crustal flow is the generation of migmatite-cored gneiss domes that riddle most orogens. High-grade rocks in many domes record pressure-temperature-time (P-T-t) paths indicating near-isothermal decompression followed by cooling from T > 700 °C to T < 350 °C in <2-5 Ma. Diapiric ascent of partially molten crust accounts for the decompression rate and magnitude required to maintain a near-isothermal path. We propose that gneiss domes are a signature of decompression and crustal melting, and are therefore fundamental structures for understanding the thermo-mechanical evolution of continental crust during orogeny.