The business of bringing new medicines to market has never been more difficult. Drug costs are a major focus for policy makers, who are pushing for changes to lower what are seen as exorbitant pharmaceutical prices. The Inflation Reduction Act (IRA), passed in 2022, promises to challenge the traditional price/volume pricing model that the pharma industry has relied on to fund continued innovation. Despite legal challenges and congressional hearings, 340B discounts and PBM practices continue to take their toll. The new presidential administration adds uncertainty, creating both potential risks and chances for new opportunities. What is certain is that the current environment calls for pharmaceutical companies to think differently about how to shape policy.