The Orlock Bridge Fault separates the Ordovician and Silurian turbidite sequences within the Southern Uplands thrust belt. A large biostratigraphical break and the 1 km wide sinistral Slieve Glah Shear Zone associated with the fault in northern Ireland led to previous interpretation as a major regional structure, possibly a terrane boundary. In Scotland, however, the stratigraphical break is much less and an association with inliers of the Moffat Shale Group suggests that the fault is essentially similar to the other tract-bounding faults which originated as syn-D1 thrusts within the imbricate stack. Localized sinistral deformation apparent along the trace of the Orlock Bridge Fault in southwestern Scotland, associated with post-1 reactivation, is comparable to that seen at Slieve Glah. Further east, a broad zone (up to 8 km) of sinistral ductile deformation, the Moniaive Shear Zone, is recognized adjacent to the Orlock Bridge Fault over a strike length of about 100 km. However, this zone differs from the Slieve Glah Shear Zone in its width and its location relative to the fault, suggesting that it is not simply related to the fault but represents a more regional deformation. Sinistral reactivation of the Orlock Bridge Fault was possibly initiated in the Wenlock during the peak of sinistral shear at the thrust front, although it may have developed over a long time contemporaneously with, but locally post-dating, the Moniaive Shear Zone. The latter deforms porphyroblasts with the thermal aureole of the c. 392 Ma Cairnsmore of Fleet granite pluton, which was emplaced into and largely post-dates the shear zone, but is deformed by the Orlock Bridge Fault. Major dip-slip reactivation of the fault post-dates the Moniaive Shear Zone and regional metamorphism and probably occurred in the Carboniferous or Permian. There is some evidence for a deep crustal feature coincident with the Orlock Bridge Fault, possibly the boundary between different crustal blocks in the collage of terrane fragments accreted during the final closure of Iapetus, which may explain the unusual extent of the reactivation of the Orlock Bridge Fault within the allochthonous Southern Uplands thrust stack. However, the situation of the fault within the Southern Uplands terrane and, in Scotland, the biostratigraphical evidence of no major stratigraphical break across the fault and the lack of any clear relationship between the Orlock Bridge Fault and the Moniaive Shear Zone indicate that the fault should not be regarded as a terrane boundary.