This study uses field, petrographic, fluid inclusion microthermometric, stable isotope and palaeomagnetic techniques to demonstrate that there have been multiple episodes of post-metamorphic, surface-derived fluids infiltrating into the crystalline basement rocks of Southwest Scotland and Northern Ireland. The timing of different episodes of regional fluid infiltration can be related to the tectonic evolution of the area. Late Caledonian faulting within the crystalline basement rocks of the Grampian Highlands and the Southern Uplands region acted as loci for the infiltration of surface-derived fluids. These earliest fluids deposited gold in the Southern Uplands and base metals and gold in the Grampian Highlands. Subsequent infiltration of surface-derived fluids within reactivated Caledonian faults in the crystalline basement rocks of Southwest Scotland and Northern Ireland during Carboniferous N-S regional extension resulted in the formation of basement-hosted, stratabound, base metal mineralization. The Highland Boundary Fault acted as a regional pathway for the penetration of post-metamorphic, surface-derived fluids in Middle Devonian, Lower Carboniferous and late Carboniferous times. Reactivated Caledonian faults in the Grampian Highlands of Scotland also acted as loci for the penetration of oxidising, meteoric fluids into shallow crustal levels during late Permian to early Triassic times. Surface-derived fluids circulating within Caledonian faults that were reactivated during the early plate separation of the North Atlantic in Triassic/Jurassic times resulted in the formation of stratabound barite mineralization in the Midland Valley and uranium mineralization in association with a post-tectonic pluton on the North Solway coast in Southern Scotland.