In 1953 DNA was shown to be a double helix of hydrogen-bonded complementary bases. Since then, knowledge of nucleic acid structures, thermodynamic stabilities, and dynamics of conformational changes has grown exponentially. This knowledge has led to the development of the biotechnology industry, the identification of plants and animals from a few cells, and many advances in the diagnosis and treatment of diseases. All the methods of physical chemistry have been used to characterize the primary structures (sequences), the secondary structures (base pairing), and the tertiary structures (folded 3D conformations) of the nucleic acids. The interactions of nucleic acids with themselves, with proteins, and with small-molecule ligands control their many functions, Novel methods are being developed to probe the structures and functions of nucleic acids. These include methods to study a single molecule and methods to select, amplify, and characterize one sequence among 10(17) different sequences.