CD8⁺ T-lymphocytes (T_CD8+) perform a critical role in immunity against tumors and virus infections. A central feature of T_CD8+ immune responses is immunodominance: the observation that T_CD8+ responses consist of a limited collection of specificities with a structured hierarchy. These immunodominance hierarchies result from a complex combination of factors. Major roles are played by peptide binding affinity, T-cell repertoire, and antigen processing and presentation. While the bulk of our information comes from mouse model systems, an increasing number of human studies suggest that immunodominance will be even more complicated. This review outlines current knowledge of T_CD8+ immunodominance to viral antigens and discusses the relevance and importance of a thorough understanding for the rational design of vaccines that elicit effective T_CD8+ responses.