This article examines the challenges in and progress of behavioral intervention research, the trajectory followed for introducing new interventions, and key considerations in protocol development. Developing and testing health-related behavioral interventions involve an incremental and iterative process to build a robust body of evidence that initially supports feasibility and safety, then proves efficacy and effectiveness, and subsequently involves translation, implementation, and sustainability in a real-world context. This process occurs over close to two decades and yields less than 14% of the evidence being integrated into practice. New hybrid models that blend test phases and involve stakeholders and end users up front in developing and testing interventions may shorten this time frame and enhance adoption of a proven intervention. Knowledge of setting exigencies and implementation challenges may also inform intervention protocol development and facilitate rapid and efficient translation into practice. Although interventions needed to improve the public’s health are complex and funding lags behind, introducing new interventions remains a critical and most worthy pursuit.