Thermo-mechanical fatigue (TMF) is a complex damage mechanism that is considered to be one of the most dominant life limiting factors in hot-section components. Turbine blades and nozzle guide vanes are particularly susceptible to this form of material degradation, which result from the simultaneous cycling of mechanical and thermal loads. The realisation of TMF conditions in a laboratory environment is a significant challenge for design engineers and materials scientists. Effort has been made to replicate the in-service environments of single crystal (SX) materials where a lifing methodology that encompasses all of the arduous conditions and interactions present through a typical TMF cycle has been proposed. Traditional procedures for the estimation of TMF life typically adopt empirical correlative approaches with isothermal low cycle fatigue data. However, these methods are largely restricted to polycrystalline alloys, and a more innovative approach is now required for single-crystal superalloys, to accommodate the alternative crystallographic orientations in which these alloys can be solidified.