Multi-photon microscopy is a powerful tool for imaging lymphocyte migration and interaction in intact biological organs. These experiments generate quantitative data on the cell motility, shape dynamics, and contact duration of cellular interactions. In this chapter we review mathematical models that have successfully contributed to the interpretation of these data with regard to lymphocyte migration and interaction. The examples involve different modelling approaches and range from T cell priming in secondary lymphoid tissue to B cell affinity maturation in germinal centres.