Cyber-physical systems (CPSs) are real-world processes that are controlled by computer algorithms. We consider CPSs where a centralized, software-based controller maintains the process in a desired state by exchanging measurements and setpoints with process agents (PAs). As CPSs control processes with low-inertia, e.g., electric grids and autonomous cars, the controller needs to satisfy stringent real-time constraints. However, the controllers are susceptible to delay and crash faults, and the communication network might drop, delay or reorder messages. This degrades the quality of control of the physical process, failure of which can result in damage to life or property. Existing reliability solutions are either not well-suited for real-time CPSs or impose serious restrictions on the controllers. In this thesis, we design, implement and evaluate reliability mechanisms for real-time CPS controllers that require minimal modifications to the controller itself. We begin by abstracting the execution of a CPS using events in the CPS, and the two inherent relations among those events, namely network and computation relations. We use these relations to introduce the intentionality relation that uses these events to capture the state of the physical process. Based on the intentionality relation, we define three correctness properties namely, state safety, optimal selection and consistency, that together provide linearizability (one-copy equivalence) for CPS controllers. We propose intentionality clocks and Quarts, and prove that they provide linearizability. To provide consistency, Quarts ensures agreement among controller replicas, which is typically achieved using consensus. Consensus can add an unbounded-latency overhead. Quarts leverages the properties specific to CPSs to perform agreement using pre-computed priorities among sets of received measurements, resulting in a bounded-latency overhead with high availability. Using simulation, we show that availability of Quarts, with two replicas, is more than an order of magnitude higher than consensus. We also propose Axo, a fault-tolerance protocol that uses active replication to detect and recover faulty replicas, and provide timeliness that requires delayed setpoints be masked from the PAs. We study the effect of delay faults and the impact of fault-tolerance with Axo, by deploying Axo in two real-world CPSs. Then, we realize that the proposed reliability mechanisms also apply to unconventional CPSs such as software defined networking (SDN), where the controlled process is the routing fabric of the network. We show that, in SDN, violating consistency can cause implementation of incorrect routing policies. Thus, we use Quarts and intentionality clocks, to design and implement QCL, a coordination layer for SDN controllers that guarantees control-plane consistency. QCL also drastically reduces the response time of SDN controllers when compared to consensus-based techniques. In the last part of the thesis, we address the problem of reliable communication between the software agents, in a wide-area network that can drop, delay or reorder messages. For this, we propose iPRP, an IP-friendly parallel redundancy protocol for 0 ms repair of packet losses. iPRP requires fail-independent paths for high-reliability. So, we study the fail-independence of Wi-Fi links using real-life measurements, as a first step towards using Wi-Fi for real-time communication in CPSs.