This textbook covers the physical properties of nucleic acid underlying the biological functions of DNA and RNA. It looks at the variety of nucleic acid structures observed in nature, thermodynamic and energetic principles that govern the formation and behavior of those structures, and the ways proteins recognize and manipulate nucleic acids. It also gives relevant experimental and computational approaches throughout the book, along with exercises. Additionally, the author presents a quantitative, practical toolkit to the principles of structure and energetics.