Glide is a ligand docking program for predicting protein-ligand binding modes and ranking ligands via high-throughput virtual screening. Glide utilizes two different scoring functions, SP and XP GlideScore, to rank-order compounds. Three modes of sampling ligand conformational and positional degrees of freedom are available to determine the optimal ligand orientation relative to a rigid protein receptor geometry. This unit presents protocols for flexible ligand docking with Glide, optionally including ligand constraints or ligand molecular similarities.