This article introduces the *phenix.real_space_refine* program, which is part of the PHENIX suite and is designed for real-space refinement of atomic models in cryo-EM and crystallography. The program uses a simplified target function that allows for fast calculation, enabling the identification of optimal data-restraint weights with minimal runtime. The refinement process incorporates additional information such as secondary structure and rotamer-specific restraints, as well as constraints on internal molecular symmetry. The effectiveness of the program is demonstrated through simulations and the re-refinement of 385 cryo-EM-derived models from the Protein Data Bank at resolutions of 6 Å or better, showing significant improvements in model quality and fit to the target maps. The article also discusses the refinement target function, the evaluation of refinement progress, and the performance of the program on simulated and real data.This article introduces the *phenix.real_space_refine* program, which is part of the PHENIX suite and is designed for real-space refinement of atomic models in cryo-EM and crystallography. The program uses a simplified target function that allows for fast calculation, enabling the identification of optimal data-restraint weights with minimal runtime. The refinement process incorporates additional information such as secondary structure and rotamer-specific restraints, as well as constraints on internal molecular symmetry. The effectiveness of the program is demonstrated through simulations and the re-refinement of 385 cryo-EM-derived models from the Protein Data Bank at resolutions of 6 Å or better, showing significant improvements in model quality and fit to the target maps. The article also discusses the refinement target function, the evaluation of refinement progress, and the performance of the program on simulated and real data.