The development of vast array of laboratory methods and their applications provided great leaps in the ability of the researchers to discover new features and functions of macro-molecules. Most of them represent procedures for measuring or visualizing ever-smaller quantities or tinier features of molecules, or part of molecules. Especially when applied in combination, these methods have led to enormous advances in understanding the structural features of proteins and nucleic acids. New techniques have been regularly introduced and the sensitivity of older techniques greatly improved upon. The originators of several of those breakthrough methods were awarded Nobel Prizes. Basic principles of some of most important techniques invented and applied in molecular biology research are described in this chapter.