Currently, most regulatory bodies use real-world data and evidence (RWD/RWE) as supportive information to evaluate the treatment safety but not effectiveness. Use of RWD/RWE in health care decision making attracts increasing attention. Retrospective/prospective observational studies leveraging electronic health data in hospital billing and medical records, as well as other clinical and administrative data, provide a broader representation of real clinical practice and patient population than those found in traditional randomized controlled trials (RCTs).The FDA's PDUFA VI has set up the timeline to publish draft guidance on usage of RWD/RWE on the evaluation of safety and the approval of additional indications of an approved product. EMA has published multiple guidance documents on conducting post-authorization safety and effectiveness studies. However, many challenges and barriers exist. Transparency and reproducibility issues of RWD/RWE are the major concerns. In this presentation, we will define RWD/RWE, illustrate the potential benefits, provide the considerations for generating the RWD/RWE with examples, discuss proposals to fit healthcare decision-making purpose.