Quality clinical trials are required to inform clinical practice and policy changes as they are the best form of evidence that can minimise the effect of bias. However, conducting clinical trials in transplantation is often challenging owing to the nature of the disease, complexity of the transplant population and the variability and heterogeneity of outcome measures. Here, our experts will discuss the potential novel trial designs, the use of novel end-points, and the ethical issues surrounding the design and conduct of clinical trials in transplantation.