The development of new drugs is currently a long and costly process in large part due to the failure of promising drug candidates identified in initial in vitro screens to perform as intended in vivo. New approaches to drug screening are being developed which focus on providing more biomimetic platforms. This review surveys this new generation of drug screening technologies, and provides an overview of recent developments in organoid culture systems which could afford previously unmatched fidelity for testing bioactivity and toxicity. The challenges inherent in such approaches will also be discussed, with a view towards bridging the gap between proof-of-concept studies and a wider implementation within the drug development community. (C) 2014 Elsevier B.V. All rights reserved.