We report on the development and validation of the OPLS4 force field. OPLS4 builds upon our previous work with OPLS3e to improve model accuracy on challenging regimes of drug-like chemical space that includes molecular ions and sulfur-containing moieties. A novel parametrization strategy for charged species, which can be extended to other systems, is introduced. OPLS4 leads to improved accuracy on benchmarks that assess small-molecule solvation and protein-ligand binding.