A survey of the Brookhaven Protein Data Bank has revealed the presence of catenated closed loops (topological links) in the structures of quinoprotein methylamine dehydrogenase, cytochrome, and human chorionic gonadotropin, and of knotted and catenated closed loops in ascorbate oxidase and human lactoferrin. All of these structures are topologically chiral. In contrast to polynucleotide knots and links in circular DNA, which are constructed entirely from the backbone polynucleotide chain, knots and links in proteins are formed from polypeptide chain segments combined with intrachain cross-links (cofactors and/or cystine disulfide bridges) that are thermodynamically but not kinetically stable. The question of whether bonds other than covalent ones are suitable for inclusion in the molecular graph of a protein is critically discussed.