There is emerging agreement that sustainability challenges require new ways of knowledge production and decision-making. One key aspect of sustainability science, therefore, is the involvement of actors from outside academia into the research process in order to integrate the best available knowledge, reconcile values and preferences, as well as create ownership for problems and solution options. Transdisciplinary, community-based, interactive, or participatory research approaches are often suggested as appropriate means to meet both the requirements posed by real-world problems as well as the goals of sustainability science as a transformational scientific field. Dispersed literature on these approaches and a variety of empirical projects applying them make it difficult for interested researchers and practitioners to review and become familiar with key components and design principles of how to do transdisciplinary sustainability research. Starting from a conceptual model of an ideal-typical transdisciplinary research process, this article synthesizes and structures such a set of principles from various strands of the literature and empirical experiences. We then elaborate on them, looking at challenges and some coping strategies as experienced in transdisciplinary sustainability projects in Europe, North America, South America, Africa, and Asia. The article concludes with future research needed in order to further enhance the practice of transdisciplinary sustainability research.