Adaptive immunity starts by antigen recognition at the periphery of the body. This function is performed by dendritic cells (DCs), leukocytes that randomly scan tissues searching for harmful particles. After encountering with a pathogenic element such as bacterial products DCs acquire the capacity to migrate to lymph nodes, function essential for the proper functioning of the immune system. In this seminar I will discuss about the cellular changes that facilitate migration of DCs between distant organs. I will show the particular actin cytoskeleton rearrangements needed for the proper displacement of DCs in the complex environments of tissues and the machinery responsible of these changes. Finally I will discuss about the physiological relevance of these discoveries in the context of health and disease.