The growth of Big Data and other innovations, such as mobile phones, the personal computer, the Internet, numerous digital sensor devices, DNA sequencing and -omics technologies, and social networks have positioned Healthcare and Biomedical Research for a “great inflection” before the end of this decade. This transformation is being driven by data, information, and the empowerment and engagement of patients. It is positioning society to move from acute care and overreliance on emergency department visits to a chronic disease-management focus, leading to a wellness, prevention, and health focus. Big data challenges in healthcare and biomedical research include: (1) data and information standardization, integration and aggregation of biological and clinical research measurements, patient-reported information, and sensor-generated data; (2) data and information privacy and health IT (HIT) security, including policies and regulations; and (3) best practices regarding data sharing and use of open-source Big Data analytics applications.