Summary: Gaining insights into the structural determinants of protein–protein interactions holds the key for a deeper understanding of biological functions, diseases and development of therapeutics. An important aspect of this is the ability to accurately predict the binding strength for a given protein–protein complex. Here we present PROtein binDIng enerGY prediction (PRODIGY), a web server to predict the binding affinity of protein–protein complexes from their 3D structure. The PRODIGY server implements our simple but highly effective predictive model based on intermolecular contacts and properties derived from non-interface surface. Availability and Implementation: PRODIGY is freely available at: http://milou.science.uu.nl/services/PRODIGY. Contact: a.m.j.j.bonvin@uu.nl, a.vangone@uu.nl