This article, which is based on a presentation at the First Annual Meeting of the American Academy of Nanomedicine, is divided into three parts. In the first, we describe naturally occurring DNA repair nanomachines, using the nanomachine that executes the nonhomologous end-joining (NHEJ) reaction for DNA double-strand break (DSB) repair as an example. In the second, we discuss therapeutic benefits that may be derived from the ability to modify the behavior of naturally occurring nanomachines, using as an example the concept of delaying DSB repair in rapidly dividing cancer cells to increase their natural sensitivity to radiation therapy. In the third part, we discuss similarities in the overall size, shape, and design of different nanomachines that manipulate DNA and RNA, and the possibility of developing nanomachines with new specificities not found in nature.