Peptide binding to major histocompatibility complex (MHC) molecules is the most selective requisite for T-cell recognition. Therefore, prediction of peptide-MHC binding is the main basis for anticipating T-cell epitopes. A very popular and accurate method to predict peptide-MHC binding is based on motif-profiles and here we show how to make them using EPIMHC (http://imed.med.ucm.es/epimhc/). EPIMHC is a database of T-cell epitopes and MHC-binding peptides that unlike any related resource provides a framework for computational vaccinology. In this chapter, we describe how to derive peptide-MHC binding motif-profiles in EPIMHC and use them to predict peptide-MHC binding and T-cell epitopes. Moreover, we show evidence that customization of peptide-MHC binding predictors can lead to enhanced epitope predictions.