Ligand conformational flexibility has long been recognized as an important issue in virtual screening (VS). To this end, a number of different methodologies have been adapted to tackle the problem. Many of said techniques were originally designed for ligand derived pharmacophore screens, but have subsequently been fashioned for application within structure-based virtual screening (SVS). A popular adaptation is the pre-calculation of diverse ligand conformations for subsequent docking in target active sites. In this paper, we study a number of the software programs currently being used in conformer generation, analyzing their ability to regenerate known ligand binding conformations. The implications of these studies are discussed, from the perspective of VS in general and SVS in particular.