The new discipline of whole systems research (WSR) targets the study of complex CAM therapies as system-level phenomena, as opposed to single-agent or uni-dimensional effects. This article describes the pre-defined goals, issues that were developed, and opportunities that were revealed in a workshop held in Vancouver BC, in which scientists, practitioners, and policy makers met to lay the foundations of WSR. Important issues were identified, such as treatment individualization, problems of diagnosis, patient-practitioner interaction, varying therapeutic contexts, and patient-determined outcome values. Research design issues that were addressed included a variety of challenges to the study of intact systems, in relation to both synergy and emergent behaviors, and the opportunities to innovate the conventional RCT. As the network of CAM scientists and practitioners engaged in WSR expands, a common nomenclature and body of techniques will help us to a better understanding of the ways in which whole systems affect healing.