Mycobacterium tuberculosis (Mtb) remains a major threat to human health worldwide. Although treatment of infection is an important part of tuberculosis control, an improved vaccine is essential for the elimination of this disease. Control of infection with Mtb is dependent on the cellular immune system, which in turn requires an understanding of those antigens that are capable of stimulating CD4+ and CD8+ T-cell responses. Peptide libraries provide a high-throughput system for identifying novel T-cell epitopes. They can also be used to assess the hierarchy of immunodominance of these novel antigens and epitopes that are associated with infection with Mtb. This T-cell-driven means of antigen discovery is well adapted to vaccine development as well as developing the tools necessary to understand the natural history of this important human pathogen.