The valves of the heart cannot regenerate spontaneously. Therefore, heart valve disease generally necessitates surgical repair or replacement of the diseased tissue by mechanical or bioprosthetic valve substitutes in order to avoid potentially fatal cardiac or systemic consequences. Although survival and quality of life is enhanced for many patients treated surgically, currently available valve substitutes remain imperfect. This is especially the case in pediatric applications, where physiologically corrective procedures can be successfully performed, but reoperations are frequently required to replace failed valve substitutes or accommodate growth of the patient. While much work is currently underway to incrementally improve existing valve substitutes, a major impact will require radically new technologies, including tissue engineering or regeneration. The use of engineered tissue offers the potential to create a non-obstructive, non-thrombogenic tissue valve substitute containing living cells capable of providing ongoing remodeling and repair of cumulative injury to the extracellular matrix. Ideally, this would allow growth in maturing recipients. The innovative fabrication of materials and the development of sophisticated methods to repair or regenerate damaged or diseased heart valves requires integration of a diverse array of basic scientific principles and enabling technologies. Thus, heart valve tissue engineering requires an understanding of relationships of structure to function in normal and pathological valves (including mechanisms of embryological development, tissue repair and functional biomechanics), and the ability to control cell and tissue responses to injury, physical stimuli and biomaterial surfaces, through chemical, pharmacological, mechanical and potentially genetic manipulations. These approaches created by advances in cell biology raise exciting possibilities for in situ regeneration and repair of heart valves.