The long, rich history of topology in mathematics has proven extremely useful for the study of DNA. DNA, the genetic blueprint for life, undergoes tremendous flux as it is packaged, replicated, segregated, transcribed, recombined and repaired. Extremely long and skinny, DNA is prone to entanglement. Every time it is copied, the two resulting "daughter chromosomes" are entangled. And nearly all organisms maintain duplex DNA in a slightly underwound state. Linking number (Lk), the major descriptor for DNA apart from base pair sequence, defines the three forms of DNA topology, which are known to biologists as knots, catenanes, and supercoils. Changes in Lk have dramatic effects on biological processes. In this talk I will provide an overview of DNA topology and the biological ramifications of topology, including exciting new developments in the application to medicine. The following authors have contributed to the work: Jonathan M. Fogg1, Daniel J. Catanese, Jr.1, Donald Schrock, II1, Richard W. Deibler1,2,3, Jennifer K. Mann1,4, De Witt L. Sumners4, Brian E. Gilbert1, Youli Zu5, Nianxi Zhao5. 1Departments of Molecular Virology & Microbiology, Biochemistry and Molecular Biology, and Pharmacology, Baylor College of Medicine, Houston, TX 77025 2Interdepartmental Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030 3Department of Systems Biology, Harvard Medical School, Boston, MA 02115 4Department of Mathematics, Florida State University, Tallahassee, FL 32306 5Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030 USA