Message design is one of the most complex and vibrant research areas in the communication discipline. Based on the preconference of the 2014 Kentucky Conference on Health Communication, this special issue of Health Communication is focused on a broad range of message design concerns. It features 10 original articles addressing topics ranging from fundamental questions related to theory and method to questions of message adaptation for translation and dissemination. Together, these articles reflect the rich variety of health behaviors addressed by health communication researchers and the breadth and depth of theoretical, methodological, and practical approaches to be considered in message design research.