A pharmacophore model does not describe a real molecule or a real association of 
functional groups but illustrates a molecular recognition of a biological target 
shared by a group of compounds. Pharmacophores also represent the spatial 
arrangement of essential interactions in a receptor-binding pocket. Structure 
based pharmacophores (SBPs) can work both with a free (apo) structure or a 
macromolecule-ligand complex (holo) structure. The SBP methods that derive 
pharmacophore from protein-ligand complexes use the potential interactions 
observed between ligand and protein, whereas, the SBP method that aims to derive 
pharmacophore from ligand free protein, uses only protein active site 
information. Therefore SBPs do not encounter to challenging problems such as 
ligand flexibility, molecular alignment as well as proper selection of training 
set compounds in ligand based pharmacophore modeling. The current review deals 
with Hot Spot' analysis of binding site to feature generation, several 
approaches to feature reduction, and considers shape and excluded volumes to SBP 
model building. This review continues to represent several applications of SBPs 
in virtual screening especially in parallel screening approach and multi-target 
drug design. Also it reports the applications of SBPs in QSAR. This review 
emphasizes that SBPs are valuable tools for hit to lead optimization, virtual 
screening, scaffold hopping, and multi-target drug design.