In this work, we examine whether Physical Unclonable Functions (PUFs) can act as lightweight security mechanisms for practical applications in the context of the Internet of Things (IoT). In order to do so, we first discuss what PUFs are, and note that memory-based PUFs seem to fit the best to the framework of the IoT. Then, we consider a number of relevant memory-based PUF designs and their properties, and evaluate their ability to provide security in nominal and adverse conditions. Finally, we present and assess a number of practical PUF-based security protocols for IoT devices and networks, in order to confirm that memory-based PUFs can indeed constitute adequate security mechanisms for the IoT, in a practical and lightweight fashion.More specifically, we first consider what may constitute a PUF, and we redefine PUFs as inanimate physical objects whose characteristics can be exploited in order to obtain a behaviour similar to a highly distinguishable (i.e., “(quite) unique”) mathematical function. We note that PUFs share many characteristics with biometrics, with the main difference being that PUFs are based on the characteristics of inanimate objects, while biometrics are based on the characteristics of humans and other living creatures. We also note that it cannot really be proven that PUFs are unique per instance, but they should be considered to be so, insofar as (human) biometrics are also considered to be unique per instance.We, then, proceed to discuss the role of PUFs as security mechanisms for the IoT, and we determine that memory-based PUFs are particularly suited for this function. We observe that the IoT nowadays consists of heterogeneous devices connected over diverse networks, which include both high-end and resource-constrained devices. Therefore, it is essential that a security solution for the IoT is not only effective, but also highly scalable, flexible, lightweight, and cost-efficient, in order to be considered as practical. To this end, we note that PUFs have been proposed as security mechanisms for the IoT in the related work, but the practicality of the relevant security mechanisms has not been sufficiently studied.We, therefore, examine a number of memory-based PUFs that are implemented using Commercial Off-The-Shelf (COTS) components, and assess their potential to serve as acceptable security mechanisms in the context of the IoT, not only in terms of effectiveness and cost, but also under both nominal and adverse conditions, such as ambient temperature and supply voltage variations, as well as in the presence of (ionising) radiation. In this way, we can determine whether memory-based PUFs are truly suitable to be used in the various application areas of the IoT, which may even involve particularly adverse environments, e.g., in IoT applications involving space modules and operations.Finally, we also explore the potential of memory-based PUFs to serve as adequate security mechanisms for the IoT in practice, by presenting and analysing a number of cryptographic protocols based on these PUFs. In particular, we study how memory-based PUFs can be used for key generation, as well as device identification, and authentication, their role as security mechanisms for current and next-generation IoT devices and networks, and their potential for applications in the space segment of the IoT and in other adverse environments. Additionally, this work also discusses how memory-based PUFs can be utilised for the implementation of lightweight reconfigurable PUFs that allow for advanced security applications. In this way, we are able to confirm that memory-based PUFs can indeed provide flexible, scalable, and efficient security solutions for the IoT, in a practical, lightweight, and inexpensive manner.