Thanks to the recent advances in computational power and algorithms, computer-aided drug design is increasingly being used to identify potential drug candidates prior to wet-lab experiment. Molecular dynamics (MD) simulations are often employed to compute drug–target stabilities and binding affinities following molecular docking in structure-based drug design (SBDD). In this review, we introduce the workflow of SBDD and focus mainly on the stability and binding affinity assessment using MD-based algorithms, including continuous MD, enhanced sampling, end-point assessment, alchemical transformations, and potential of mean force calculations. This work aims to offer an overview over the commonly used MD simulation methods and discusses advantages and limitations.