Precision medicine based on molecular profiling is moving from the realm of clinical utility studies towards standard of care. There remain, however, significant technological and implementation challenges that need to be addressed to ensure the widespread access to high complexity tests. These challenges include the provision of high quality, scalable assays that can be offered in clinically meaningful timeframes and at a cost that does not limit adoption. In addition, the computational and analytical environments must exist to host, compute, and deliver the increasingly large data sets created for each patient. There needs to be agreement on best practices and specifications for performance of secondary analysis tools (variant callers) across all classes of clinically meaningful variant categories. And, there needs to be education and training of a large network of variant review scientists, clinical geneticists, and molecular pathologists on variant interpretation and classification. This presentation will contemplate these challenges, highlight areas where progress has been made, and where more has yet to be done.