Driven by technology scaling, integrated systems become more susceptible to various causes of random hardware faults such as radiation-induced soft errors. Such soft errors may cause malfunction of the system due to corruption of data or control flow, which may lead to unacceptable risks for life or property in safety-critical applications. Hence, safety-critical systems deploy protection techniques such as hardening and redundancy at different layers of the system stack (circuit, logic, architecture, OS/schedule, compiler, software, algorithm) to improve resiliency against soft errors. Here, cross-layer resilience techniques aim at finding lower cost solutions by providing accurate estimation of soft error resilience combined with a systematic exploration of protection techniques that work collaboratively across the system stack. This chapter demonstrates how to apply the cross-layer resilience principle on custom processors, fixed-hardware processors, accelerators, and SRAM memories (with a focus on soft errors) and presents key insights obtained.