A premise in health promotion and disease prevention is that exposure to and consequences of illness and injury can be minimized through people’s actions. Health campaigns, broadly defined as communication strategies intentionally designed to encourage people to engage in the actions that prevent illness and injury and promote wellbeing, typically try to inspire more than one person to change. No two people are exactly alike with respect to their risk for illness and injury or their reactions to a campaign attempting to lower their risk. These variations between people are important for health messaging. Effective campaigns provide a target audience with the right persuasive strategy to inspire change based on their initial state and psychosocial predictors for change. It is often financially and logistically unreasonable to create campaigns for each individual within a population; it is even unnecessary to the extent to which people exist in similar states and share psychosocial predictors for change. A challenging problem for health campaigns is to define those who need to be reached, and then intelligently group people based on a complex set of variables in order to identify groups with similar needs who will respond similarly to a particular persuasive strategy. The premise of this chapter is that segmentation at its best is a systematic and explicit process of research to make informed decisions about how many audiences to consider, why the audience is doing what they are doing, and how to reach that audience effectively.