DNA is a living molecule, writhing, twisting and bending in response to the physical forces applied to it by genetic processes. Twisting and untwisting of the double helix by powerful molecular motors generates, at least transiently, high levels of torques. Although under relaxed conditions the double helical B-form is the predominant conformation of DNA, in response to physical stress, B-DNA strains inhomogeneously, adopting a variety of alternative structures. These structures are the sites of genetic damage that increase the fragility of the genome, but they may also participate in physiological processes performing functions not achievable using conventional duplex. The dynamic response of DNA to supercoiling forces contributes to control of genes such as c-myc whose physiological levels must be precisely regulated.