The use of tissue-engineering methods to create autologous heart valve constructs has the potential to overcome the fundamental drawbacks of more traditional valve prostheses. Traditional mechanical valves, while durable, increase the risk for endocarditis and thrombogenesis, and require the recipient to continue lifelong anticoagulant therapy. Homograft or xenograft heart valve prostheses are associated with immune reaction and progressive deterioration with limited durability. Most importantly, neither option is capable of growth and remodeling in vivo and both options place the patient at risk for valve-related complications and reoperation. These shortcomings have prompted the application of tissue-engineering techniques to create fully autologous heart valve replacements. Future clinically efficacious tissue-engineered autologous valves should be nonthrombogenic, biocompatible, capable of growth and remodeling in vivo, implantable with current surgical techniques, hemodynamically perfect, durable for the patient's life and most importantly, significantly improve quality of life for the patient. In order to meet these expectations, the nature of the ideal biochemical milieu for conditioning an autologous heart valve will need to be elucidated. In addition, standardized criteria by which to quantitatively evaluate a tissue-engineered heart valve, as well as noninvasive analytical techniques for use in long-term animal models, will be required. This article highlights the advances, challenges and future clinical prospects in the field of tissue engineering of autologous heart valves, focusing on progress made by studies that have investigated a fully autologous, tissue-engineered pulmonary valve replacement in vivo.