There is a well-documented gap between research and practice in many areas of behavioral medicine. This gap is due in part to limitations in the capacity of the research database to address questions that are of central concern to clinicians, administrative decision makers, and policymakers. Thus, there has been a call for “practical clinical trials” that compare clinically viable alternative interventions and assess multiple outcomes important for clinical and policy decisions in diverse patient populations and settings. Such trials offer great potential, and they raise interesting challenges regarding optimal research design and source of funding. We discuss issues related to practical clinical trials in behavioral medicine, propose a need for practical behavioral trials (PBTs), and describe design features that will facilitate clinical and policy decision making. This type of PBT can help to close the gap between research and practice and advance the field of evidence-based behavioral medicine. We discuss potential challenges and objections to PBTs and conclude by providing recommendations for the design, conduct, reporting, and review of practical trials.