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The development of the heart and vessels during embryogenesis depends on the complex interplay of various cell types and growth factors. The implementation of molecular tools has enabled us to analyze early steps in cardiogenesis and vasculogenesis. Furthermore the introduction of transgenic and knock-out techniques in mice, and the miniaturization of physiologic measurements to the mouse level has fundamentally changed our knowledge. Pathophysiology can be unraveled at the molecular level. The implications of various stimuli on specific membrane receptors can be analyzed. In response to receptor activation, interacting intracellular signaling pathways can activate or block transcription factors. The changes in gene expression lead to functional changes observed in the cardiovascular systems of animal models and humans. Changes in the level of gene expression and protein function in cardiovascular disease are discussed for the sarcomeric, calcium handling and ion channel genes. Furthermore, different approaches to the design of cell-type-specific gene therapy approaches for the heart and vessels are outlined.