PrimeX is a new X-ray crystal structure refinement program for biological macromolecules from Schrödinger, Inc. It produces an all-atom model at moderate resolution that is in excellent agreement with the diffraction data and that is also suitable for immediate use in computational chemistry applications. The program features maximum-likelihood reciprocal-space minimization, simulated-annealing refinement, ligand placement, loop building and side-chain placement. PrimeX is integrated with the powerful molecular-graphics program Maestro, which provides an easy-to-use graphical interface. Command-line access to PrimeX tools provides for their scripting into complex workflows. Additional information about these features and the methods used therein are presented.