Research using human fresh functional tissue represents one of the fastest growing areas of drug discovery and development. There are two key drivers in the use of functional tissues: firstly, the need to reduce clinical attrition rates by understanding human pharmacology during preclinical testing, and secondly, the drive towards biomarkers for personalised medicine. The dominant approach to drug development, based on primary screening in high-throughput models and secondary screening in animals, has previously produced numerous ‘blockbuster’ drugs, but clinical attrition rates of 95% are no longer viewed as sustainable. Human disease-relevant tissue is increasingly viewed as a way to decrease clinical failures, particularly during phase II and III where poor efficacy has been partly attributed to an over-reliance on animal models. Fresh, intact, functional human tissue assays aim to bridge the gaps between in vitro cell-based studies, in vivo animal studies and clinical trials. Such tissues offer advantages over simpler cell-based models, avoid species differences and truly reflect the diverse patient population. This chapter reviews the challenges and benefits of using functional tissues in drug development, including procedures for sourcing tissue, common techniques and examples of how data from functional tissues is used to predict clinical effects.