Protein-protein interactions (PPIs) offer the unique opportunity to tailor ligands aimed at specifically stabilizing or disrupting the corresponding interfaces and providing a safer alternative to conventional ligands targeting monomeric macromolecules. Selecting biologically relevant protein-protein interfaces for either stabilization or disruption by small molecules is usually biology-driven on a case-by-case basis and does not follow a structural rationale that could be applied to an entire interactome. We herewith provide a first step to the latter goal by using a fully automated and structure-based workflow, applicable to any PPI of known three-dimensional (3D) structure, to identify and prioritize druggable cavities at and nearby PPIs of pharmacological interest. When applied to the entire Protein Data Bank, 164 514 druggable cavities were identified and classified in four groups (interfacial, rim, allosteric, orthosteric) according to their properties and spatial locations. Systematic comparison of PPI cavities with pockets deduced from druggable protein-ligand complexes shows almost no overlap in property space, suggesting that even the most druggable PPI cavities are unlikely to be addressed with conventional drug-like compound libraries. The archive is freely accessible at http://drugdesign.unistra.fr/ppiome .