Handwashing with soap is a highly effective method for reducing the risk of diarrheal disease, yet interventions to alter this behavior often fail or achieve only short-term success. In this paper, we propose that the “science of habit” can partly explain the challenge of handwashing behavior change. Integrating basic science insights from psychology, cognitive science, and behavior change research, we propose six principles for creating greater initiation and maintenance of handwashing change. For each principle, we outline the supporting science and provide examples of potential tactical implementation in field settings. In addition, we highlight ways in which habit thinking can be integrated with interventions that focus on more reflective, conscious drivers of change such as knowledge, social norms, and strong emotions.