Background There is an increasing need for a worldwide professional integration of conventional medicine and traditional/complementary whole medical systems (WMSs). However, the integration is perceived by conventional medicine as problematic or unacceptable, because of a supposed lack of evidence for specific effects of WMSs therapies and supposed prescientific or unscientific paradigms of WMSs. Objectives To review the literature on the features of WMSs, similarities and differences between conventional medicine and WMSs, and scientific and clinical practice issues that should be dealt with in order to promote the integration process. Methods A critical, narrative review of the literature on six WMSs. Results and Conclusions Key factors for the integration of WMSs and conventional medicine are as follows: legal frameworks, quality standards, high-quality research on safety and efficacy of WMS interventions, infrastructure, and financial resources. For scientific assessment of WMSs, there are unresolved ontological, epistemological, and methodological issues and issues of diagnostics, therapy delivery, and outcome assessment in clinical practice. Future research not only should be directed at quality assurance and generating the necessary data on safety and efficacy/effectiveness but also should address more fundamental (ontological, epistemological, and methodological) issues, in order to overcome the differences between WMSs and conventional medicine.