In line with its aim to decarbonize the EU’s building stock by 2050, the May 2018 amendment to the Energy Performance of Buildings Directive calls for “research into… the energy performance of historic buildings… while also safeguarding and preserving cultural heritage.” To date in the UK, research in this field has focused on solid masonry construction. The research in this paper explores the previously under-researched retrofit of historic timber-framed buildings. In situ monitoring highlights that in some instances, the combination of incompatible materials, flawed detailing, poor workmanship and lack of controlled ventilation can facilitate biological attack. Digital hygrothermal simulations suggest that orientation, climatic conditions and infill material all significantly influence hygrothermal behavior, however, no prolonged periods of conditions favorable to biological decay were identified. Initial monitoring of test panels under laboratory conditions supports these results, however further long term monitoring is required and is currently underway, funded by Historic England.