Polymorphonuclear neutrophils (PMNs) and monocyte/macrophages (MMs) are professional phagocytic cells that are able to phagocytose and destroy infectious agents. Therefore, they are key anti-infectious actors in host defense but can mediate tissue damages. In addition, it is now clear that the role of these cells goes far beyond phagocytosis and pathogen killing. PMNs and MMs are essential cells for immunity, absolutely required to build and modulate the innate response. The respective roles of PMNs and MMs in the inflammatory process are discussed: their common features and their differences are reviewed, both in terms of origins and functions with special emphasis on novel concepts about neutrophil survival and resolution of inflammation. The recognition and the subsequent engulfment of apoptotic PMNs by macrophages is a key event of the resolution of inflammation, which can be associated with autoimmunity or inflammatory diseases. During the past years, significant efforts have been made to dissect the molecular mechanisms governing phagocytosis and pathogen killing. Although these effector functions are crucial, more work has to be done to understand the respective role of PMNs and MMs to regulate and inhibit the inflammatory process as well as the immune response. This might be the future challenge for the next years in phagocyte research and this will presumably open new avenues of research in the modulation of inflammation.