The development of the Midland Valley of Scotland from Silurian times is re-examined. Earlier (Cambro-Ordovician) terrane accretion of the Midland Valley Terrane to the Laurentian continent by sinistral strike-slip continued to control basin development, sedimentary facies distribution and deformation from Llandovery through to at least early Devonian times. A widespread Mid- to Late-Wenlock strike-slip event has been recognised. This event is variable in its effect, but may indicate a direct link between the Midland Valley, Southern Uplands and Grampian terranes, suggesting that the terranes were juxtaposed by Mid-Wenlock times. In the Midland Valley this event was followed by a renewed phase of basin development with the deposition of ?Pridoli-Lower Devonian clastic sediments which was interrupted by the Lower Devonian volcanic event. There was a shift northwards in the focus of Lower Devonian basin development which was accompanied by a diachronous deformation event across the Midland Valley which resulted in inversion/uplift from early to middle Devonian times. This phase of deformation, uplift and erosion may be related to end-Caledonian transpression.