Electrostatics plays a fundamental role in virtually all processes involving biomolecules in solution. The Poisson–Boltzmann equation constitutes one of the most fundamental approaches to treat electrostatic effects in solution. The theoretical basis of the Poisson–Boltzmann equation is reviewed and a wide range of applications is presented, including the computation of the electrostatic potential at the solvent‐accessible molecular surface, the computation of encounter rates between molecules in solution, the computation of the free energy of association and its salt dependence, the study of pKa shifts and the combination with classical molecular mechanics and dynamics. Theoretical results may be used for rationalizing or predicting experimental results, or for suggesting working hypotheses. An ever‐increasing body of successful applications proves that the Poisson–Boltzmann equation is a useful tool for structural biology and complementary to other established experimental and theoretical methodologies. Copyright © 2002 John Wiley & Sons, Ltd.