As the health-care industry grapples with high costs and system-wide complexity, new entrants and established players alike are shaking up a value chain ripe for disruption. In the biopharmaceutical ecosystem, organizations are creating new financial tools and business models to unlock alternative sources of capital and ensure that valuable science progresses for patients. Hospital systems and nonprofits are entering the arena, promising to reduce costs and shortages for medicine. For care delivery, large corporate employers are forming alliances to improve care and reduce costs—potentially upending traditional players such as payers and providers. Why so much change? Who will come out on top? And what changes are we likely to see in the next two to three years?