Tissue engineering aims at building 3-dimensional living substitutes that are equal to or better than the damaged tissue to be replaced. The development of such a tissue replacement requires a multidisciplinary approach and careful attention to the optimal cell source, the interactions of growth factors and extracellular milieu, and the scaffolding design. This article is a review of the tissue engineering programs of the National Heart, Lung, and Blood Institute, which support research efforts to translate novel approaches for the treatment of cardiovascular disease. Recent progress is discussed, which highlights some major questions relevant to cardiovascular tissue engineering. The National Heart, Lung, and Blood Institute has a strong interest in tissue engineering and will continue to foster the practical, clinical, and commercial development of research discoveries in this emerging field.