Bridging scales from atomic resolution to entire cells is a technical and computational challenge. Over the past decade, crosslinking mass spectrometry (CLMS) has developed into a robust and flexible tool that provides medium-resolution structural information. CLMS data provide a measure of the proximity of amino acid residues and thus offer information on the folds of proteins and the topology of their complexes. Here, we highlight notable successes of this technique as well as common pipelines. Novel CLMS applications, such as in-cell crosslinking, probing conformational changes and tertiary-structure determination in complex mixtures, are now beginning to make contributions to molecular biology and the emerging fields of structural systems biology and interactomics.