Pharmacophore approaches have evolved to be one of the most successful tools in 
drug discovery, especially since the past two decades. 3D pharmacophore methods 
are now commonly used as part of more complex workflows in drug discovery 
campaigns, and have been successfully and extensively applied in virtual 
screening (VS) approaches. This review provides a perspective of how to assess 
the performance of 3D pharmacophore models to be used in VS. Since 3D VS 
protocols are in general assessed by their ability to discriminate between 
active and inactive compounds, we summarize the impact of the composition and 
preparation of modeling and external sets on the outcome of evaluations. 
Moreover, we highlight the significance of both classic enrichment parameters 
and advanced descriptors for the performance of 3D pharmacophore-based virtual 
screening methods.