This paper summarizes the discussions held during the First IEEE Life Sciences Grand Challenges Conference, held on October 4-5, 2012, at the National Academy of Sciences, Washington, DC, and the grand challenges identified by the conference participants. Despite tremendous efforts to develop the knowledge and ability that are essential in addressing biomedical and health problems using engineering methodologies, the optimization of this approach toward engineering the life sciences and healthcare remains a grand challenge. The conference was aimed at high-level discussions by participants representing various sectors, including academia, government, and industry. Grand challenges were identified by the conference participants in five areas including engineering the brain and nervous system; engineering the cardiovascular system; engineering of cancer diagnostics, therapeutics, and prevention; translation of discoveries to clinical applications; and education and training. A number of these challenges are identified and summarized in this paper.