Over the last couple of decades the success rates for drug development have fallen significantly across all therapeutic areas, including oncology. Since 2011 though, seven new cancer medicines have been approved by the FDA (vismodegib, bentuximab vedotin, vandetanib, crizotinib, ipilimumab, vemurafenib, abiraterone). The pattern emerging from the successfully developed drugs is that increasing proportions are targeted to patient populations where cancer growth is driven by a pathway specifically inhibited by the drug. The emerging deeper understanding of molecular drivers of cancer through technology improvements and cost reductions in next generation sequencing has presented opportunities to create new approvable development paths for novel therapeutic agents. However, these same opportunities also present challenges which require adaptation of the ‘traditional' drug development route - starting from Phase I. Success requires good understanding of the driving biology, the right preclinical models, understanding of the limitations of these models, and close collaboration between drug developers, diagnostic developers, translational investigators and regulatory bodies. This session will discuss how the approach to drug development has changed since the time when gefitinib was taken through Phase I to Phase III development; the challenges this presents to recruit patients into early-phase clinical trials which include patient selection; the challenges required to get simultaneous regulatory approval of a companion diagnostic and a drug; and a look to how these challenges can be overcome.