In this Perspective, David Spring from the University of Cambridge, UK, and colleagues discuss strategies and recent success stories in the field of diversity-oriented synthesis. Here, Dr Spring gives a brief overview of the area. 

1. Please explain, for a non-specialist, the significance of your article. 

In this article we explore the current understanding of what chemicals can be made, and how we can evaluate how different they are from each other. This is important because drug discovery has been underperforming lately. Is this because the pharmaceutical industry has been looking in the wrong place for drugs? Can we explore other regions of so called chemical space to find new drugs, or chemical tools? We explore pathways to access this space in the best possible way. 

2. What has motivated you to conduct this work? 

We are excited by using a chemical approach to explore biology. At one extreme this is drug discovery and the potential therapeutic benefits that we could enable are an obvious motivation. To do this we need more chemicals, and we need them to be different from each other, yet be drug-like. This is a real challenge to modern day synthetic chemistry. On the journey we need to understand what chemical diversity means, and this is an intellectual challenge. 

3. Where do you see this work developing in the future? 

The field is in its infancy. We need more examples of compound discovery using this method. In the same way that combinatorial chemistry was over-hyped, then under-hyped, it has reached a rational phase of understanding. It took over 10 years to discover a new drug using combinatorial chemistry, but it is now accepted that the approach is standard. Diversity oriented synthesis is slowly approaching this rational phase, so we feel it is undervalued at the moment. We hope this paper will highlight the potential and the exciting challenges ahead, and improve the education of chemists to rise to the challenge.