Novelty is central to the study of memory, but the wide range of experimental manipulations aimed to reveal its effects on learning produced inconsistent results. The novelty/encoding hypothesis suggests that novel information undergoes enhanced encoding and thus leads to benefits in memory, especially in recognition performance; however, recent studies cast doubts on this assumption. On the other hand, data from animal studies provided evidence on the robust effects of novelty manipulations on the neurophysiological correlates of memory processes. Conceptualizations and operationalizations of novelty are remarkably variable and were categorized into different subtypes, such as stimulus, context, associative or spatial novelty. Here, we summarize previous findings about the effects of novelty on memory and suggest that predictive coding theories provide a framework that could shed light on the differential influence of novelty manipulations on memory performance. In line with predictive coding theories, we emphasize the role of unexpectedness as a crucial property mediating the behavioral and neural effects of novelty manipulations.