Continued research is critical to build upon past improvements in mortality and morbidity from cancer. Provisions in the Patient Protection and Affordable Care Act (PPACA) of 2010 address health research that affect cancer research in many positive and some potentially negative ways. The impact of PPACA on cancer research must be viewed in the context of the federal economic situation and the ongoing reform of the American clinical trial system. Major components of PPACA affect cancer research including requiring insurance coverage of standard care provided as part of clinical trials, establishment and funding of the Patient Centered Outcomes Research Institute focused on comparative effectiveness research, and establishment of the Cures Acceleration Network to foster rapid translation of basic research to the bedside. This article reviews these programs, their strengths, and our concerns regardingtheir potential shortfalls and areas needed to support cancer research on which PPACA is silent.