Breakthrough therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. There have been over 150 breakthrough therapy designation requests since the Food and Drug Administration Safety and Innovation Act (FDASIA) was signed into law on July 9, 2012. This presentation will provide an analysis of the breakthrough therapy designation submissions, for those that have been granted as well as for those that have been denied; share some cases of breakthrough therapy approvals in oncology; and discuss the opportunities and challenges with this new program.