*Presagia AI (OccamPoint Partner member)The landmark approvals of pembrolizumab for the treatment of patients whose tumors have high microsatellite instability and larotrectinib and entrectinib for those harbouring NTRK fusions, have marked the beginning of the era of histology-agnostic drug development in oncology. However, the path to regulatory approval in the space remains complex due to the potential for heterogeneous histologies and continued emergence of new data. This review summarizes the development of approved drugs and drug candidates in the space and discusses considerations for developing histology-agnostic indications from the biological, regulatory, and statistical point of view.