Over the last fifty years, small has emerged as the new big thing. The reduction of information and electronics to nanometer dimensions has revolutionized science, technology, and society. Now scientists and engineers are creating physical machines that operate at the nanoscale. Using approaches ranging from lithographic patterning to the co-opting of biological machinery, new devices are being built that can navigate, sense, and alter the nanoscale world. In the coming decades, these machines will have enormous impact in fields ranging from biotechnology to quantum physics, blurring the boundary between technology and life. © 2012 by the American Academy of Arts & Sciences.