INTRODUCTION: Despite advances in tobacco dependence treatment in the past two decades, progress has been inconsistent and slow. This paper reviews pervasive methodological issues that may contribute to the lack of timely progress in tobacco treatment science including the lack of a dynamic model or framework of the cessation process, inefficient study designs, and the use of distal outcome measures that poorly index treatment effects. The authors then present a phase-based cessation framework that partitions the cessation process into four discrete phases based on current theories of cessation and empirical data. These phases include: (1) Motivation, (2) Precessation, (3) Cessation, and (4) Maintenance. DISCUSSION: Within this framework, it is possible to identify phase-specific challenges that a smoker would encounter while quitting smoking, intervention components that would address these phase-specific challenges, mechanisms via which such interventions would exert their effects, and optimal outcome measures linked to these phase-specific interventions. Investigation of phase-based interventions can be accelerated by using efficient study designs that would permit more timely development of an optimal smoking cessation treatment package.