This dissertation advances a vision of Personal Health Informatics (PHI), a class of tools that can leverage personal data to support health self-management. Today, a powerful combination of factors is coming together that can facilitate the creation of these technologies and amplify their benefits. Namely, the world is awash in data, software and sensors continue to capture more, increasingly capable algorithms are helping humans make sense of it all, and ubiquitous devices (that people are keen to use to manage their wellness) can deliver this information via individually-tailored, insight-enabling, personally-empowering, health-enhancing feedback. A central argument of this dissertation is that domain knowledge can help drive PHI development in order to fully capitalize on the potential of these technologies. A central contribution of this dissertation is a framework for engaging in domain-driven development. In specifying this reusable development pattern, I provide guidance on moving through stages of domain inquiry, domain-driven health assessment, and domain-aware intervention design. To begin, I describe what domain knowledge encompasses, why it is valuable, and how to synthesize insights from diverse sources in order to gain an appreciation of the role technology can play in a given context. I then explain how this understanding can inform research goals, strategies for assessing significant health determinants, and implications for designing effective interventions. To demonstrate this process in practice, I present my own research as a case study on developing domain-driven technology that supports healthy sleep, daily performance, and emotional wellbeing. Overall, I argue that a domain-driven approach that foregrounds a deep understanding of a targeted aspect of health, together with a compassion for the lived experiences of users, will produce technological solutions that better meet individual needs and promote more positive outcomes.