Fifth-generation and beyond (5G and xG) wireless networks are envisioned to meet the requirements of vertical applications like high traffic throughput, ultra-massive connectivity, extremely low latency, and high quality of service. Disruptive technologies, such as massive multiple-input multiple-output, millimeter wave, and multiple access are being deployed to meet these requirements. However, their deployment poses several challenges, including a lack of network transparency, management decentralization, and reliability. Moreover, the heterogeneity of future networks raises security concerns, e.g., confidentiality, privacy, and trustworthiness. Indeed, due to the emergence of novel paradigms, e.g., quantum computing, traditional security approaches are no longer sufficient to protect over-the-air communications. Hence, 5G/xG networks must consider smart security techniques to operate seamlessly and efficiently. Within this context, physical layer security (PLS) and blockchain represent promising solutions to complement existing methods. By exploiting the characteristics of wireless links, PLS can enhance the security of communications, while blockchain may enable networks’ decentralization, integrity, and trustworthiness. Motivated by these advancements, we provide an in-depth review of the existing PLS and blockchain literature. Then, for the first time in the literature, we present a framework to integrate PLS with blockchain in 5G/xG systems. We first provide a thorough discussion about the potential of PLS and blockchain for 5G/xG systems. Then, we present our vision of a cross-layer architecture that leverages PLS and blockchain. Through a case study, we demonstrate the high potential of cross-layer design to improve the security of vehicular networks. Finally, we identify related challenges and shed light on future research directions.