The prevailing methods to predict T-cell epitopes are reviewed. Motif matching, matrix, support vector machine (SVM), and empirical scoring function methods are mainly reviewed; and the thermodynamic integration (TI) method using all-atom molecular dynamics (MD) simulation is mentioned briefly. The motif matching method appeared first and developed with the increased understanding of the characteristic structure of MHC-peptide complexes, that is, pockets aligned in the groove and corresponding residues fitting on them. This method is now becoming outdated due to the insufficiency and inaccuracy of information. The matrix method, the generalization of interaction between pockets of MHC and residues of bound peptide to all the positions in the groove, is the most prevalent one. Efficiency of calculation makes this method appropriate to scan for candidates of T-cell epitopes within whole expressed proteins in an organ or even in a body. A large amount of experimental binding data is necessary to determine a matrix. SVM is a relative of the artificial neural network, especially direct generalization of a linear Perceptron. By incorporating non-binder data and adopting encoding that reflects the physical properties of amino acids, its performance becomes quite high. Empirical scoring functions apparently seem to be founded on a physical basis. However, the estimates directly derived from the method using only structural data are far from practical use. Through regression with binding data of a series of ligands and receptors, this method predicts binding affinity with appropriate accuracy. The TI method using MD requires only structural data and a general atomic parameter, that is, force field, and hence theoretically most consistent; however, the extent of perturbation, inaccuracy of the force field, the necessity of an immense amount of calculations, and continued difficulty of sampling an adequate structure hamper the application of this method in practical use.