Nanostructure field-effect transistors (nano-FETs) including isolation layers formed between epitaxial source/drain regions and semiconductor substrates and methods of forming the same are disclosed. In an embodiment, a semiconductor device includes a power rail, a dielectric layer over the power rail, a first channel region over the dielectric layer, a second channel region over the first channel region, a gate stack over the first channel region and the second channel region, where the gate stack is further disposed between the first channel region and the second channel region and a first source/drain region adjacent the gate stack and electrically connected to the power rail.