Runtime/reconfigurable architectures based on Field-Programmable Gate Arrays (FPGAs) are a promising augment to conventional processor architectures such as Central Processing Units (CPUs) and Graphic Processing Units (GPUs). Since the reconfigurable parts are typically manufactured in the latest technology, they may suffer from aging and environmentally induced dependability threats. In this chapter, strategic online test methods for dependable runtime-reconfigurable architectures as well as cross-layer optimizations for high reliability and lifetime are developed. Firstly, two orthogonal online tests are proposed that ensure reliable configuration of the reconfigurable fabric and aid fault detection. Secondly, a novel design method called module diversification is presented that enables self-repair of the system in case of faults caused by degradation effects as well as single-event upsets in the configuration. Thirdly, a novel stress-aware placement method is proposed that aims for slowing down system degradation by aging effects. The combined methods ensure reliable operation across architectural and gate level and allow to prolong the lifetime of dependable runtime-reconfigurable architectures.