The confirmation of developmental differences between tissue macrophages and peripheral monocytes has changed our view of the functions and dynamics of these two important components of the innate immune system. It has been demonstrated conclusively that homeostasis of tissue resident macrophages is maintained by a low proliferative turn over. During an inflammatory response, bone marrow derived monocytes enter the tissue in large numbers and take part in the defense against the pathogens. After the destruction of invading pathogens, these cells disappear and tissue resident macrophages can be detected again. This new appreciation of the innate immune response has not only answered many outstanding questions regarding the role of the different myeloid cell types in inflammation, but also opened up new areas of research relating to the tissue- and pathogen-specific fate of the inflammatory macrophages or dendritic cells (DCs), and the transfer of this knowledge from mouse models to the human immune system. Nevertheless, there is still confusion in infection models, and especially in studies of human infections, as to what extent these recent observations and findings influence previous interpretations of data. This review will focus on insights from mouse models, summarize the literature on the ontogeny of macrophages and monocytes, explain the role of frequently used monocyte markers and effector molecules, and finally, discuss the role of inflammatory monocytes/macrophages/DCs in two experimental parasitic diseases.