In this book, Nobel Laureate Arieh Warshel introduces the microscopic basis of electrostatic theory and the ways to evaluate electrostatic energies in macromolecules. Warshel rigorously develops the theoretical framework of electrostatics, introducing a hierarchy of models from all-atom representations to continuum approximations, critically evaluating their assumptions and limitations.A major focus is placed on the electrostatic underpinnings of enzymatic catalysis, protein-ligand interactions, redox processes, and the folding and stability of proteins. The text also addresses specialized topics such as pKa calculations, ion and proton channels, and the dielectric behavior of proteins. Furthermore, we examine the electrostatic basis of molecular machines, signaling mechanisms (including G-proteins and Ras), GPCR activation, and cell-cell interactions.By integrating detailed theoretical models with biological function, Warshel provides a unifying perspective that reshapes our understanding of biomolecular action. This work serves as both a definitive reference and a forward-looking framework, emphasizing the predictive power of physically consistent electrostatic models in elucidating life at the molecular level.