Advances in genomics and human genetics have enabled a more detailed understanding of the impact of genetics in a disease and its treatment. In addition to a patient's clinical signs and symptoms, physicians can now or in near future consider genetic data for their diagnosis and treatment decisions. This new information source based on genome and gene expression analysis makes clinical decision processes even more complex. Beyond, behavioral and environmental aspects should also be considered in order to realize personalized medicine. Given these additional information sources, the need for support in decision making is increasing. In this paper, we introduce a vision how knowledge-based systems or decision support systems can help to realize personalized medicine and we explore the upcoming challenges for clinical decision support in that context.