In the second half of the 20th century, the United States enjoyed stature and prosperity at levels seldom achieved in recorded history. The country's status included predominance in most fields of science and technology (S&T), as well as a phenomenal breadth and pace of innovation. We are now experiencing a global shift to a more level playing field among nations; demographics, economics, and political forces are the driving forces behind this shift. The impact of this shift on U.S. S&T will be significant. By the middle of the 21st century, it is likely that a number of nations will be similarly prosperous and technologically productive. No single nation or group will dominate as the United States did in the latter half of the 1900s. The U.S. share of the global S&T enterprise will decrease, and only a small fraction of U.S. scientists and engineers (S&E) will work on national security problems. This change poses challenges to the roles and conduct of Department of Defense (DOD) S&T. In particular, DOD's ability to maintain an authoritative awareness of S&T developments around the world will become increasingly problematic. Most attempts to quantify these challenges utilize simple linear or exponential extrapolations. Although such approaches are helpful for short-term predictions, they tend to produce unrealistically pessimistic predictions for the timescales considered in this paper. The present work establishes an empirical relationship between an economy's gross domestic product (GDP) per capita and its ability to gene rate S&T knowledge. This paper then employs the results of a full economic analysis for the period 2005-2050 to estimate the S&T knowledge production for each of the world's 17 largest economies. The estimate indicates that U.S. share of S&T productivity will decline from about 26 percent in 2005 to 18 percent in 2050. This decline, while problematic, is not unmanageable. At least through 2050, the United States will remain one of the world's most significant contributors to scientific knowledge. As a result, the U.S. S&T workforce should be large enough, relative to the world S&T workforce, to remain cognizant of S&T developments around the world-although the means of doing so may change. This ability to remain cognizant is important because by 2050, countries other than the United States will produce most scientific knowledge. Maintaining an authoritative awareness of S&T around the world will be essential if the United States is to remain economically and militarily competitive. This awareness includes the ability of the U.S. S&T workforce to authoritatively interpret trends in global S&T. The required awareness can be maintained only if the U.S. S&T workforce is a participant in the global S&T community. This is true for the DOD S&T workforce as well. For DOD to succeed, it will be necessary to find a means to tap the knowledge of the larger U.S. S&T community regarding global S&T. It is only at this level that the United States will have a sufficient number of S&T "brain cells" to actually know what is occurring in the world of global S&T, what is important, and what is not important. Tapping this knowledge will be very challenging for DOD. Nevertheless, we must ensure the global S&T knowledge held by the larger U.S. S&T community is available to the military and that DOD has the internal capability to comprehend and exploit this knowledge through the DOD S&T workforce. The term "DOD S&T workforce" refers to those S&Es who are funded by DOD S&T dollars that fall into the categories of Basic Research (6.1) and Exploratory Development (6.2). This workforce is larger than the DOD federal S&T workforce (often called the in-house workforce), which, of course, has a special role. Some members of the DOD S&T workforce will be employees of DOD; others will be involved through vehicles such as contracts, advisory committees, and cooperative programs with other government agencies.