As immunotherapies to treat malignancy continue to diversify along with the tumor types amenable to treatment, it will become very important to predict which treatment is most likely to benefit a given patient. Tumor neoantigens, novel peptides resulting from somatic tumor mutations and recognized by the immune system as foreign, are likely to contribute significantly to the efficacy of immunotherapy. Multiple in silico methods have been developed to predict whether peptides, including tumor neoantigens, will be presented by the major histocompatibility complex (MHC) Class I or Class II, and interact with the T cell receptor (TCR). The methods for neoantigen prediction will be reviewed here, along with the most important examples of their use in the field of oncology.