Community health workers (CHWs) are increasingly being incorporated into health programs because they are assumed to effectively deliver health messages in a culturally relevant manner to disenfranchised communities. Nevertheless, the role of CHWs—who they are, what they do, and how they do it—is tremendously varied. This variability presents a number of challenges for conducting research to determine the effectiveness of CHW programs, and translating research into practice. We discuss some of these challenges and provide examples from our experience working with CHWs. We call for future research to identify the “core elements” of effective CHW programs that improve the health and well-being of disenfranchised communities.