The federal 340B Drug Pricing Program has expanded rapidly, with important yet still unmeasured impact on both managed care practice and policies. Notably, providers increasingly rely on external, contract pharmacies to extend 340B pricing to a broad set of patients. In 2014, 1 in 4 U.S. retail, mail, and specialty pharmacy locations acted as contract pharmacies for 340B-covered entities. This commentary discusses crucial ways in which 340B growth is affecting managed care pharmacy through formulary rebates, profits from managed care paid prescriptions, disruption of retail pharmacy networks, and reduced generic dispensing rates. Managed care should become more engaged in the discussion on how the 340B program should evolve and offer policy proposals to mitigate the challenges being encountered. There is also an urgent need for objective, transparent research on the 340B program's costs, benefits, and implications for managed care pharmacy and practice.