Myeloid leukocytes are the first line of host defence. When they sense perturbations in tissue homeostasis such as infection, inflammation and ischemia, they respond by trafficking. Whilst neutrophils and macrophages migrate to sites of infection, dendritic cells (DC) migrate from tissue-resident sites back into lymph nodes where they activate T and B lymphocytes. The directed migration of these leukocytes through peripheral tissues is thus crucial for their function. This article considers recent advances in our understanding of the adhesive and motile behaviour of macrophages and DC, with particular emphasis on the podosomes that appear to be required for normal migration through extracellular matrices.