Although knowledge of a protein's functional site is a key requirement for understanding its mode of action at the molecular level, our ability to locate such sites experimentally is far exceeded by the rate at which sequence and structural information is being accumulated. siteFiNDER|3D is an online tool for the prediction of functionally important regions in proteins of known structure. At the core of the server lies the CFG analysis algorithm, which uses a moving 3D window to correlate patterns of functional/chemical group conservation in the query protein with the location of functional sites. Here, we give a general overview of the functionality offered by the siteFiNDER|3D server, along with general recommendations aimed at maximizing the accuracy and predictive value of this tool in a variety of contexts. siteFiNDER|3D can be accessed at: 'http://sage.csb.yale.edu/sitefinder3d' and requires, at a minimum, the atomic coordinates of a query protein in PDB format.