For over 60 years, inoculation theory has been a key framework to understand resistance to persuasion, yet many critical questions have remained unanswered. This dissertation aims to provide a theoretical and empirical understanding of how resistance to persuasion effects decay over time. In the context of resistance to persuasion by misinformation, I offer 10 empirical experiments that shed new light on this question, including several methodological innovations. In Chapter 2, I propose a new model that integrates memory theories with motivation theories on inoculation. In Chapters 3–6, I evaluate the long-term effectiveness of inoculation in message-based, gamified, and video-based inoculation interventions, unveiling the underlying mechanisms of decay. In Chapter 7, I address methodological issues, including the effects of repeated testing, and unstandardised items, and the development of a new misinformation susceptibility test. In summary, this thesis advances our understanding of the mechanisms of decay in resistance to persuasion, and sheds light on the role of and interplay between memory and motivation. The new memory-motivation model brings a significant advancement to the field, as it taps into the memory literature of forgetting—a domain in cognitive psychology—to shed new light on a concept in social psychology, and enables a new approach to modelling the longevity of inoculation effects. In addition, I offer novel insights into limitations with current methodological paradigms, and demonstrate how new standardised measurement tools can be developed to more accurately map inoculation effects in future research. Finally, I discuss how the findings of this dissertation can inform not only inoculation scholarship, but also intervention designers, evaluators, and policy makers, on how to address the problem of misinformation, and demonstrate how to extend the long-term effects of inoculation in applied interventions.