Protein surface regions with similar physicochemical properties and shapes may perform similar functions and bind similar binding partners. Here we present two web servers and software packages for recognition of the similarity of binding sites and interfaces. Both methods recognize local geometrical and physicochemical similarity, which can be present even in the absence of overall sequence or fold similarity. The first method, SiteEngine (http:/bioinfo3d.cs.tau.ac.il/SiteEngine), receives as an input two protein structures and searches the complete surface of one protein for regions similar to the binding site of the other. The second, Interface-to-Interface (I2I)-SiteEngine (http:/bioinfo3d.cs.tau.ac.il/I2I-SiteEngine), compares protein-protein interfaces, which are regions of interaction between two protein molecules. It receives as an input two structures of protein-protein complexes, extracts the interfaces and finds the three-dimensional transformation that maximizes the similarity between two pairs of interacting binding sites. The output of both servers consists of a superimposition in PDB file format and a list of physicochemical properties shared by the compared entities. The methods are highly efficient and the freely available software packages are suitable for large-scale database searches of the entire PDB.