The use of thin-gauge, light-weight structures in combination with the severe aero-thermodynamic loading makes reusable hypersonic cruise vehicles prone to fluid-thermal-structural interactions. These interactions result in surface perturbations in the form of temperature changes and deformations that alter the stability and eventual transition of the boundary layer. The state of the boundary layer has a significant effect on the aerothermodynamic loads acting on a hypersonic vehicle. The inherent relationship between boundary-layer stability, aerothermodynamic loading, and surface conditions make the interaction between the structural response and boundary-layer transition an important area of study in high-speed flows. The goal of this dissertation is to examine the interaction between boundary layer transition and the response of aerothermally compliant structures. This is carried out by first examining the uncoupled problems of: (1) structural deformation and temperature changes altering boundary-layer stability and (2) the boundary layer state affecting structural response. For the former, the stability of boundary layers developing over geometries that typify the response of surface panels subject to combined aerodynamic and thermal loading is numerically assessed using linear stability theory and the linear parabolized stability equations. Numerous parameters are examined including: deformation direction, deformation location, multiple deformations in series, structural boundary condition, surface temperature, the combined effect of Mach number and altitude, and deformation mode shape. The deformation-induced pressure gradient alters the boundary-layer thickness, which changes the frequency of the most-unstable disturbance. In regions of small boundary-layer growth, the disturbance frequency modulation resulting from a single or multiple panels deformed into the flowfield is found to improve boundary-layer stability and potentially delay transition. For the latter, transitional boundary-layer aerothermodynamic load models are developed and incorporated into a fundamental aerothermoelastic code to examine the impact of transition onset location, transition length and transitional overshoot in heat flux and fluctuating pressure on the response of panels. Results indicate that transitional fluid loading can produce larger thermal gradients, greater peak temperatures, earlier flutter onset, and increased strain energy accumulation as compared to a panel under turbulent loading. Sudden transition, with overshoot in heat flux and fluctuating pressure, occurring near the leading edge of the panel provides the most conservative estimate for determining the life of the structure. Finally, the coupled interaction between boundary-layer transition and structural response is examined by enhancing the aerothermoelastic solver to allow for time-varying transition prediction as a function of the panel deformation and surface temperature. A kriging surrogate is developed to reduce the online computational expense associated with transition prediction within an aerothermoelastic simulation. For the configurations examined in this study, panel deformation has a more dominant effect on boundary-layer stability than surface temperature. Allowing for movement of the transition onset location results in characteristically different panel deformations due to spatial variation in the thermal bending moment. The response of the clamped panel is more sensitive to the transition onset location than the simply-supported panel.