The induction of an adaptive immune response is an essential step in the generation of long-lasting, protective immunity to pathogens. Many studies over the last few decades have identified the cell populations involved in the generation of antigen-specific immunity and elucidated the role of many important molecules. However, because of the low precursor frequency of antigen-specific cells, the immune system must be highly dynamic, surveying most sites of the body. Recent studies have, therefore, begun to examine how the cells of the immune system interact in vivo during the induction of an immune response, identifying new and important roles for certain molecules and revealing how previously unrecognised alterations in cell-cell interactions can have significant implications for the resulting immune response. Here we review some of these recent studies that provide a valuable insight into the mechanisms involved in the induction of immunity.