Epitopes, in the context of T cell recognition, are short peptides typically derived by antigen processing, and presented on the cell surface bound to MHC molecules (HLA molecules in humans) for TCR scrutiny. The identification of epitopes is a context-dependent process, with consideration given to, for example, the source pathogen and protein, the host organism, and state of the immune reaction (e.g., following natural infection, vaccination, etc.). In the following review, we consider the various approaches used to define T cell epitopes, including both bioinformatic and experimental approaches, and discuss the concepts of immunodominance and immunoprevalence. We also discuss HLA polymorphism and epitope restriction, and the resulting impact on the identification of, and potential population coverage afforded by, epitopes or epitope-based vaccines. Finally, some examples of the practical application of T cell epitope identification are provided, showing how epitopes have been valuable for deriving novel immunological insights in the context of the immune response to various pathogens and allergens.