The implementation of the Patient Protection and Affordable Care Act will profoundly impact cancer care. Its components will influence multiple levels of the health-care environment including states, communities, health-care organizations, and individuals seeking care. To illustrate these influences, two reforms are considered: 1) accountable care organizations and 2) insurance-based reforms to gather evidence about effectiveness. We discuss these reforms using three facets of multilevel interventions: 1) their intended and unintended consequences, 2) the importance of timing, and 3) their implications for cancer care and research. Successful implementation of multilevel interventions depends on understanding the political setting and goals of health-care reform.