ELASPIC is a novel ensemble machine-learning approach that predicts the effects of mutations on protein folding and protein–protein interactions. Here, we present the ELASPIC webserver, which makes the ELASPIC pipeline available through a fast and intuitive interface. The webserver can be used to evaluate the effect of mutations on any protein in the Uniprot database, and allows all predicted results, including modeled wild-type and mutated structures, to be managed and viewed online and downloaded if needed. It is backed by a database which contains improved structural domain definitions, and a list of curated domain–domain interactions for all known proteins, as well as homology models of domains and domain–domain interactions for the human proteome. Homology models for proteins of other organisms are calculated on the fly, and mutations are evaluated within minutes once the homology model is available.