The genomic revolution lifts up several potential opportunities in predictive and preventive medicine. Yet, genomic medicine opportunities can lead to clinical utility only if challenges that come with it are understood, anticipated, and faced. This review discusses the challenges that genomic medicine raises for the patients and their physicians, the general population, study participants and investigators. The article presents a program of genomic consultation in general internal medicine in the French-speaking part of Switzerland (MedOmics) that aims to address these challenges in order to optimize the clinical opportunities offered by genomic medicine.