The Activation Model of Information Exposure highlights the potential for individual differences in arousal in response to information, as well as the consequences of these patterns for information processing and seeking. Over the past 2 decades, the theoretical approach has generated considerable research in health communication. Most applications, however, have focused on substance use among adolescents and young adults. In this article, we assess the relevance of the activation approach for cancer communication. Although a wide range of communication efforts related to cancer prevention and treatment stand to benefit from acknowledgement of individual differences in optimal levels of arousal, we also acknowledge issues and challenges that remain for work on the Activation Model and sensation seeking. In reaching this conclusion, we explore some limitations of the Activation Model in its current form and point to new directions for future research.