Cyber-physical systems, that consist of a cyber part a computing System and a physical part the system in the physical environment as well as the respective interfaces between those parts, are omnipresent in our daily lives. The application in the physical environment drives the overall requirements that must be respected when designing the computing system. Here, reliability is a core aspect where some of the most pressing design challenges are: *monitoring failures throughout the computing system, *determining the impact of failures on the application constraints, and *ensuring correctness of the computing system with respect to application-driven requirements rooted in the physical environment. *This chapter gives an overview of the state-of-the-art techniques developed within the Horizon 2020 project IMMORTAL that tackle these challenges throughout the stack of layers of the computing system while tightly coupling the design methodology to the physical requirements. (The chapter is based on the contributions of the special session Designing Reliable Cyber-Physical Systems of the Forum on Specification and Design Languages (FDL) 2016.)