Immune surveillance by T cells requires antigen presentation by molecules encoded by MHC (major histocompatibility complex) class I and class II genes in a process termed MHC restriction. MHC restriction is defined as a process in which protein antigens are proteolytically processed to short peptides, which are assembled with MHC molecules, and then displayed as peptide-bound MHC molecules at the surface of cells. Therefore, knowledge of peptide antigens presented by MHC molecules can yield information on the sources of tumor antigens, ways to track T cell responses to tumors, and targets for cancer vaccines and cell therapies. This chapter provides an overview of cancer antigens, their sources, and the mechanisms by which cells generate and present such antigens.