Important advances have occurred in research on the prevention of depression, which is an important public health concern. The present article outlines several key questions regarding the efficacy of depression prevention programs that need to be addressed before moving on to effectiveness and dissemination. Of greatest concern is that even among the most efficacious depression prevention programs, effect sizes have been small to moderate and the effects generally have not endured. Determining how particular interventions work will facilitate efficient dissemination of the active ingredients. First, however, it is crucial to establish that an intervention works, for whom programs are most and least efficacious and why, and then to modify programs accordingly. Based on the extent of questions that remain, we conclude that “we are not there yet,” although we have the beginnings of a good road map for getting there.