To increase access and improve system quality and efficiency, President Obama signed the Patient Protection and Affordable Care Act with sweeping changes to the nation's health-care system. Although not intended to be specific to cancer, the act's implementation 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. The success of complex health reforms requires understanding the scientific basis and evidence for carrying out such multilevel interventions. Conversely and equally important, successful implementation of multilevel interventions depends on understanding the political setting and goals of health-care reform.