BACKGROUND AND PURPOSE: Interventions are effective in promoting health behavior change to the extent that (a) intervention strategies modify targets (i.e., mechanisms of action), and (b) modifying targets leads to changes in behavior. To complement taxonomies that characterize the variety of strategies used in behavioral interventions, we outline a new principle that specifies how strategies modify targets and thereby promote behavior change. We distinguish two dimensions of targets-value (positive vs. negative) and accessibility (activation level)-and show that intervention strategies operate either by altering the value of what people think, feel, or want (target change) or by heightening the accessibility of behavior-related thoughts, feelings, and goals (target activation). METHODS AND RESULTS: We review strategies designed to promote target activation and find that nudges, cue-reminders, goal priming, the question-behavior effect, and if-then planning are each effective in generating health behavior change, and that their effectiveness accrues from heightened accessibility of relevant targets. We also identify several other strategies that may operate, at least in part, via target activation (e.g., self-monitoring, message framing, anticipated regret inductions, and habits). CONCLUSIONS: The Activation Vs. Change Principle (AVCP) offers a theoretically grounded and parsimonious means of distinguishing among intervention strategies. By focusing on how strategies modify targets, the AVCP can aid interventionists in deciding which intervention strategies to deploy and how to combine different strategies in behavioral trials. We outline a research agenda that could serve to further enhance the design and delivery of interventions to promote target activation.