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In 2011, the American Institute for Medical and Biological Engineering (AIMBE) (www.aimbe.org) celebrated its 20th anniversary by undertaking to identify major societal challenges to which medical and biological engineers can contribute solutions in the next 20 years. This report is a summary of the six major challenges that were identified. The report also discusses some specific areas within these high-level challenges that can form the basis for policy action, provides a brief rationale for pursuing those areas, and discusses roadblocks to progress. The six overarching challenges are: 1) engineering safe and sustainable water and food supply, 2) engineering personalized health care, 3) engineering solutions to injury and chronic diseases, 4) engineering global health through infectious disease prevention and therapy, 5) engineering sustainable bioenergy production, and 6) engineering the 21st century US economy. While arrived at independently by AIMBE, many of the elements overlap with similar challenges identified by other bodies. The similarities highlight the central mission of medical and biological engineers, working with other experts, which is to solve important problems central to human health and welfare.