Cys2-His2 (C2H2) zinc finger domains were originally identified as DNA binding domains, and uncharacterized domains are typically assumed to bind DNA. However, a growing body of evidence suggests an important and widespread role for these domains in protein binding. Over 100 C2H2 zinc finger-protein interactions have been described. This study uses common bioinformatics tools to identify sequence features that predict a DNA- or protein-binding function. Several issues, including uncertainties about the full functional capabilities of the zinc fingers, complicated these efforts. Therefore, an unbiased approach which directly examined the potential for zinc fingers to facilitate DNA or protein interactions was used to determine the full functional capabilities of the C2H2 domains in two model proteins, human OLF-1/EBF associated zinc finger (OAZ) protein and Zif268. OAZ contains 30 zinc fingers in six clusters, some of which have been previously indicated in DNA or protein interactions. Zif268 is a well-known DNA binding protein with three C2H2 domains. DNA binding was assessed using a target site selection (CAST) assay, and protein binding was assessed using a yeast two-hybrid assay. Results indicate that clusters known to bind DNA could facilitate specific protein interactions, but clusters known to bind protein did not facilitate specific DNA interactions, indicating that DNA binding is a more restricted function of zinc fingers than has previously been recognized. These results also suggest that the role of C2H2 zinc finger domains in protein interactions has probably been underestimated. The implication of these findings for the prediction of zinc finger function is discussed.