For long, protein complexes were defined by unambiguous, static contacts. Recent results, however, indicate that residues, which do not adopt a well-defined structure even in bound form, can critically influence selectivity or binding affinity via transient, dynamic interactions. This phenomenon is termed as fuzziness. Using various recently characterized examples, I’ll describe how fuzzy complexes form and the benefits of structural ambiguity in both protein-protein and protein-DNA interactions. The dynamic segments can modulate conformational preferences or flexibility of the interface, vary the spacing of the binding motif(s) or serve as a competitive partner. Post-translational modifications and/or additional interactions of structurally heterogeneous regions provide further means to regulate the activity of the complex and expand the functional repertoire of the proteins involved. Genome-wide analysis of tissue-specific alternatively spliced isoforms indicate a connection between fuzzy complexes and context-dependent functioning of proteins.