The machine learning techniques are playing a vital role in the field of immunoinformatics. In the past, a number of methods have been developed for predicting major histocompatibility complex (MHC)-binding peptides using machine learning techniques. These methods allow predicting MHC-binding peptides with high accuracy. In this chapter, we describe two machine learning technique-based methods, nHLAPred and MHC2Pred, developed for predicting MHC binders for class I and class II alleles, respectively. nHLAPred is a web server developed for predicting binders for 67 MHC class I alleles. This sever has two methods: ANNPred and ComPred. ComPred allows predicting binders for 67 MHC class I alleles, using the combined method [artificial neural network (ANN) and quantitative matrix] for 30 alleles and quantitative matrix-based method for 37 alleles. ANNPred allows prediction of binders for only 30 alleles purely based on the ANN. MHC2Pred is a support vector machine (SVM)-based method for prediction of promiscuous binders for 42 MHC class II alleles.