Palliative care practice requires excellent communication between the patient, family, and clinical team. Experts in the field have proposed a variety of communication interventions that can be used in the palliative care setting. However, these interventions are at a high level of generality: the specifics of each intervention are not well codified; the individual steps in each intervention are not easily reproducible and thus not comparable between practitioners; the methods to measure adherence to these communication protocols have not been established; and there is little detail on how to adapt these general interventions to the individual patient and family. Therefore, we lack good evidence for the efficacy of these recommendations. This paper makes the case for development of structured, testable approaches to communication that will inform clinical practice and communication training. To do so, palliative care communication should be conceived as a formal medical and psychosocial intervention-a potential treatment with risks and benefits to be systematically researched and operationalized in the same manner as medication interventions. As we illustrate, psychotherapy research has faced the same challenges in the past and has utilized manualized treatments to meet its goals. Through such approaches, we can begin to address the most basic intervention questions such as protocol efficacy, dose-response, side effects, and the optimal process and content of communication with the patient and family. The advantages of manualized communication approaches; some concepts underlying manual construction; and challenges to extending manualized communication to the palliative care domain are discussed.