In recent decades, constraining the timing of shear activity has been one of the main topics of research about the tectono-metamorphic evolution of orogenic belts. We present a review of a combined structural and geochronological approach to two major ductile regional shear zones, in two collisional orogens: the first one affecting the Variscan basement in northern Sardinia (Italy) and the External Crystalline Massifs of the Alps (East Variscan Shear Zone; EVSZ), and the second one deforming the medium- to high-grade rocks of the metamorphic core of the Himalaya (High Himalayan Discontinuity). High-resolution, texturally and chemically controlled monazite geochronology applied in separated shear zones of the Variscan belt allowed recognizing a similar timing of activity ranging between c. 340–330 and 300 Ma. This approach led to a better understanding of the evolution of the EVSZ, supporting a model where several branches were active according to a growth by linkage model. Following a similar approach, in situ U-Th-Pb analysis of monazite constrained the timing of top-to-the-S/SW shearing of a regional-scale High Himalayan Discontinuity in the Himalayan belt to between c. 28 Ma and 17 Ma. Earlier exhumation of the hanging wall was triggered by shear zone activity, whereas at the same time, the footwall was still experiencing burial with increasing P-T conditions. The timing of shearing of this shear zone fits with an in-sequence shearing tectonic model for the exhumation of the Himalayan mid-crust.