In the last years we have learned a lot about the pathopysiology of a cluster of the diseases called Metabolic Syndrome but currently an exciting discussion debates the Metabolic Syndrome in a light of a mystery of medicine or a clinical paradigm with a controversary about diagnostic, treatment or preventive procedure. There is now convincing evidence that prevention is the most important and effective way to reduce the personal and socio-economic burden of the Metabolic Syndrome and its associated complications. Still, it is currently not clear how to implement preventive interventions into clinical practice but will require an integrated and transdisciplinary approach on an international level in order to efficiently reduce premature morbidity and mortality. Nevertheless, global strategies are still lacking but are needed to tackle inequalities in health between industrialized countries and the developing world. A global health strategy has to take into account political, epidemiological, environmental, infrastructural and genetic aspects. The Metabolic Syndrome is not a mystery - it is a clinical paradigm and global challenge.