The global biotechnology revolution offers a profusion of promising innovations for the US Department of Defense (DoD). As with other emerging technologies, the commercial market, rather than defense, is driving the evolution of biotechnology products, and the ability to harness biotechnology for defense benefits has been hampered by strategic confusion in DoD. Here we describe a set of high-level challenges and a set of potential solutions that could bring innovative biotechnology closer to reality for the warfighter and DoD writ large.