Cigarette smoking is the largest preventable cause of death and morbidity in the United States. Heightened recognition of this public health concern has led researchers from multiple and varied disciplines to address this complex and multidimensional behavior. The need for an alternative research paradigm, focusing on a transdisciplinary approach that integrates work across disciplines in order to advance the field most quickly, has been identified. This recognized need led to the development of the Transdisciplinary Tobacco Use Research Centers (TTURC) initiative, funded jointly by the National Cancer Institute, the National Institute on Drug Abuse, and The Robert Wood Johnson Foundation. This paper discusses the formation and early implementation stages of the initiative, including meetings that led to the development of the TTURCs, funders' and research centers' perspectives on implementation, and early observations about the products of the initiative.