Binuclear metal centers in metalloenzymes are involved in a number of hydrolytic, hydration, isomerization, and redox processes. Despite the growing number of studies elucidating their structure, properties, and function, questions regarding certain aspects of the bimetallic proteins' biochemistry still remain, e.g., the following: (i) What are the general characteristics of binuclear sites found in 3D structures such as the range of metal-metal distances and the most common ligand bridging the two metal cations? (ii) How does the presence of a metal cation in one of the binuclear sites affect the metal-binding affinity/selectivity of the other site? (iii) How do the characteristics and metal-binding affinity/selectivity of binuclear sites compare with those of their mononuclear counterparts? Here we address these questions by combining a Protein Data Bank survey of binuclear sites with density functional theory (DFT) combined with continuum dielectric method (CDM) calculations. The results reveal that, for homobinuclear sites, the metal separation depends on the metal's charge and electron-accepting ability, and Asp(-)/Glu(-), bidentately bound to the two cations, is the most common bridging ligand. They also reveal that Mg2+ occupying one of the binuclear sites attenuates the metal-binding affinity but enhances the selectivity of its neighboring site, compared to the corresponding mononuclear counterparts. These findings are consistent with available experimental data. The weak metal binding of one of the binuclear sites would enhance the metal cofactor mobility in achieving the transition state, whereas the enhanced selectivity of Mg2+-Mg2+ centers helps protect against unwanted substitutions by transition metal ions, which are generally stronger Lewis acids compared to Mg2+.