Conspectus Electrostatic interaction plays a significant role in determining many properties of biomolecules, which exist and function in aqueous solution, a highly polar environment. For example, proteins are composed of amino acids with charged, polar, and nonpolar side chains and their specific electrostatic properties are fundamental to the structure and function of proteins. An important issue that arises in computational study of biomolecular interaction and dynamics based on classical force field is lack of polarization. Polarization is a phenomenon in which the charge distribution of an isolated molecule will be distorted when interacting with another molecule or presented in an external electric field. The distortion of charge distribution is intended to lower the overall energy of the molecular system, which is counter balanced by the increased internal energy of individual molecules due to the distorted charge distributions. The amount of the charge redistribution, which characterizes the polarizability of a molecule, is determined by the level of the charge distortion. Polarization is inherently quantum mechanical, and therefore classical force fields with fixed atomic charges are incapable of capturing this important effect. As a result, simulation studies based on popular force fields, AMBER, CHARMM, etc., lack the polarization effect, which is a widely known deficiency in most computational studies of biomolecules today. Many efforts have been devoted to remedy this deficiency, such as adding additional movable charge on the atom, allowing atomic charges to fluctuate, or including induced multipoles. Although various successes have been achieved and progress at various levels has been reported over the past decades, the issue of lacking polarization in force field based simulations is far from over. For example, some of these methods do not always give converged results, and other methods require huge computational cost. This Account reviews recent work on developing polarized and polarizable force fields based on fragment quantum mechanical calculations for proteins. The methods described here are based on quantum mechanical calculations of proteins in solution, but with a different level of rigor and different computational efficiency for the molecular dynamics applications. In the general approach, a fragment quantum mechanical calculation for protein with implicit solvation is carried out to derive a polarized protein-specific charge (PPC) for any given protein structure. The PPC correctly reflects the polarization state of the protein in a given conformation, and it can also be dynamically changed as the protein changes conformation in dynamics simulations. Another approach that is computationally more efficient is the effective polarizable bond method in which only polar bonds or groups can be polarized and their polarizabilities are predetermined from quantum mechanical calculations of these groups in external electric fields. Both methods can be employed for applications in various situations by taking advantage of their unique features.