In this chapter, practical concepts and guidelines are provided for the use of molecular dynamics (MD) simulation for the refinement of homology models. First, an overview of the history and a theoretical background of MD are given. Literature examples of successful MD refinement of homology models are reviewed before selecting the Cytochrome P450 2J2 structure as a case study. We describe the setup of a system for classical MD simulation in a detailed stepwise fashion and how to perform the refinement described in the publication of Li et al. (Proteins 71:938-949, 2008). This tutorial is based on version 11 of the AMBER Molecular Dynamics software package (http://ambermd.org/). However, the approach discussed is equally applicable to any condensed phase MD simulation environment.