Transdisciplinary research involves the integration of measures and methods across diverse response systems and levels of analysis, with that integration occurring via a synthesis of theories and models of different scientific disciplines. This paper first discusses the need for transdisciplinary research. The paper then articulates a model to guide the comprehensive evaluation of treatments for tobacco use and discusses how transdisciplinary research might be integrated into this treatment evaluation model. The potential benefits and costs of a transdisciplinary approach are discussed, along with selected research projects from the Transdisciplinary Tobacco Use Research Centers.