Safety-net hospitals have long played an essential role in the US health care system. The Affordable Care Act fundamentally changes the health care landscape and safety-net hospitals need to make major changes to compete. This report examines four safety-net hospitals to learn how they are preparing for health reform. While hospitals were employing strategies with different intensities, we found that the study hospitals had implemented an array of financial strategies focused on tapping Medicaid revenues. They also adopted delivery systems reforms, particularly ones related to developing community-based partners, and implemented changes in hospital leadership and management structure as well as efforts to better align physician incentives with hospitals and altering the culture of patient care to be more responsive to the shifting market.