Therapies designed to target cancers that harbor specific molecular signatures have reshaped the landscape of oncologic drug development, and advances in next generation sequencing have led to an increase in the identification of these alterations across tumor types. Tumor-agnostic trial designs, such as the "basket trial," have been developed as an approach to study the efficacy of these treatments and increase patient access, especially for patients whose tumors carry these alterations infrequently. We review key aspects of these genomically enriched trial strategies and their impact on drug development and approval.