Molecular investigation of tissue obtained from patients with many chronic illnesses is becoming increasingly important. Using the example of childhood cancer, we show how such investigations contribute in important ways to understanding the underlying pathophysiological basis of disease, determining optimal patient management, and identifying targets for potential new novel therapeutic approaches. Tissue banks are now recognized as an important resource for biomedical research in this area. Challenges for the future of tissue-banking include formalization of technical matters, including the generation of standard operating procedures and quality-control methods. More complex challenges attend the legal and ethical issues in tissue banking. Notwithstanding recent UK legislation, there are many legal uncertainties. Use of excised tissue in research is often claimed to raise a range of ethical issues, but it is not at all clear that public confidence and support for tissue-based research is as negative as some accounts in the socio-anthropological and ethical literature would suggest. Nonetheless, ensuring confidence and trust in tissue-banking will remain an important objective, and the possibilities of novel governance structures should be explored.