The article provides an overview of empirical force fields used in the study of biological macromolecules, emphasizing their role in investigating structure-activity relationships at an atomic level. The success of these methods is attributed to the quality of the force fields and algorithmic advancements that enhance the accuracy of simulations. The author discusses the potential energy functions commonly used in biomolecular force fields, including bond, angle, dihedral, and nonbonded interactions. The article also covers the implementation of these force fields, solvation models, and the transferability of force fields to a wide range of organic molecules of pharmacological interest. Additionally, it addresses the challenges in simulating "heterogeneous" biomolecular systems and the limitations of current models in treating electronic polarizability. The review highlights the importance of proper optimization of parameters and the need for combining rules to ensure accurate and consistent results across different force fields. The article concludes with a survey of force fields commonly used for proteins, nucleic acids, lipids, and carbohydrates, providing insights into their applicability and limitations.The article provides an overview of empirical force fields used in the study of biological macromolecules, emphasizing their role in investigating structure-activity relationships at an atomic level. The success of these methods is attributed to the quality of the force fields and algorithmic advancements that enhance the accuracy of simulations. The author discusses the potential energy functions commonly used in biomolecular force fields, including bond, angle, dihedral, and nonbonded interactions. The article also covers the implementation of these force fields, solvation models, and the transferability of force fields to a wide range of organic molecules of pharmacological interest. Additionally, it addresses the challenges in simulating "heterogeneous" biomolecular systems and the limitations of current models in treating electronic polarizability. The review highlights the importance of proper optimization of parameters and the need for combining rules to ensure accurate and consistent results across different force fields. The article concludes with a survey of force fields commonly used for proteins, nucleic acids, lipids, and carbohydrates, providing insights into their applicability and limitations.