Despite extended international efforts, the mechanisms governing T-cell receptor repertoire selection and kinetics in response to foreign or tumour antigens remain poorly characterized. A central goal of current research is to develop improved, reliable, immunological monitoring methods that measure and combine such parameters as the frequency of antigen-specific T cells and their functional capacities, as well as their clonal expansion during immune responses. Detecting and tracking defined anti-viral- and anti-tumour-specific T-cell responses ex vivo should lead to improvements in therapeutic strategies against viral infection or cancer in the future. During the past few years, highly sensitive tools have been developed to enable the molecular dissection and tracking of clonal T-cell expansion in animal models as well as in humans.