This book develops a statistical mechanical analysis of the stability of biological macromolecules. The author's approach is valid both for the long time-scale needed for DNA bond disruption, and also for highly cooperative transitions needed to explain helix melting. Prohofsky develops a new theoretical approach for executing macromolecule calculations. In particular the author devises a method for describing chemical bond disruption in these large systems, which is then used to determine when the helix melts and how drugs can dissociate from the helix. The author finds melting temperatures to be in excellent agreement with experimental observations.