The high cost of specialty pharmaceuticals is driving change across the healthcare system, including consequences for life science research and development investments, employer benefit designs, payer approaches to prior authorization and step therapy, and provider priorities for consolidation and expansion. Markups on prescription drugs refer to providers being reimbursed for products at higher amounts than product acquisition costs. Payers have been actively working to reduce prescription drug markups, but such efforts should balance possible savings with the need for thoughtful consumer protections and transparency. Policies must also be structured to promote health equity by keeping the risks to patients with lower incomes and fewer social supports front and center as they may have the greatest challenges navigating these policies.