Aggressive technology scaling and strong demand for lowering supply voltage impose a serious challenge in achieving robust and energy-efficient circuit operation. This paper first overviews on device-circuit interactions to enable cross-layer resiliency, and energy optimization. We show that the ability to monitor and control device and circuit characteristics not only increase energy-efficiency by more than 20% but also relax the severe design constraints, which were required because of the uncertainties of variability. We then demonstrate two proof-of-concept circuits in a 65 nm process to show variability resiliency and energy optimization with local body biasing.