Across rehabilitation, there is a shortage of treatments that have demonstrated efficacy and effectiveness through rigorously controlled clinical trials. Although rehabilitation efficacy and effectiveness research present many of the obstacles that are found in research on other biomedical domains, they also present a number of obstacles that are specific to the conceptual framework underlying rehabilitation practice. In this article, I review the specific challenges presented by the need to rigorously define the research participants, the treatment under investigation, and the outcomes by which treatment response will be measured. I also suggest research that will be necessary to surmount some of these obstacles.