Complexation of Histidine residues by chelated transition metal ions can be exploited for noncovalent, reversible labeling of His-tagged proteins. While the affinity of individual transition metal ions complexed by nitrilotriacetic acid (NTA) is not sufficient for stable fluorescence labeling, this problem has been overcome by multivalent NTA, which bind His-tagged proteins with subnanomolar affinity and complex lifetimes of >1 h. Selective labeling with a defined stoichiometry is possible in cell lysates and on the surface of living cells. Thus, rapid labeling in situ with these relatively small probes at low concentration is possible, which can be reversed under mild conditions.