Leukocyte function-associated molecule 1 (LFA-1) is an integrin that plays a major role in the immune system. Recent findings demonstrate that LFA-1 has a two-way signaling function, mediating cell adhesion and stimulating intracellular processes at the same time. Here, Marijke Lub, Yvette van Kooyk and Carl Figdor discuss the 'inside-out' and 'outside-in' signaling properties of LFA-1, as a prototype leukocyte integrin, in normal and malignant T cells. They integrate data into a model that highlights the role of the cytoskeleton in the regulation of LFA-1.