Real-World Evidence (RWE) holds out the promise of reducing time and costs of product approvals, identifying new uses for existing products, increasing our ability to treat rare diseases, and improving clinical practices for using drugs and medical devices. The 21st Century Cures Act, enacted in 2016, requires FDA to evaluate the use of RWE in approving new drug indications. FDA in 2017 issued a final guidance document regarding RWE in regulatory decisions involving medical devices. The private sector is also focusing on RWE: more than half the pharmaceutical companies in a recent survey say they are significantly expanding their involvement in RWE. Nonetheless, misunderstandings and uncertainties remain, both about what constitutes RWE and its potential role in regulatory and other aspects of precision medicine.