Polymorphonuclear neutrophil granulocytes (PMN) are considered the most important cells of the host immune response against bacterial challenge. The functional mechanism of PMN consists of different steps: tethering, rolling, primary adhesion to the vascular wall, firm adhesion to the activated endothelium in the inflamed region, trans-migration across endothelium, chemotaxis, contact with the bacterium and phagocytosis and, finally, killing of the micro-organism by releasing hydrolytic enzymes and/or by production of toxic substances such as free radicals. Each of these steps is controlled by interactions between cells and many components of the immune system or inflammatory mediators. These interactions generate specific signals, important for cell regulation. Recent technological advances in molecular biology and immunobiology allowed to disclose the precise role of various molecules involved in the immune response, that regulate PMN function; conversely, more factors have been identified, whose role is still unknown. In the process of adhesion, for example, many classes of molecules are involved (selectins, integrins, ICAMs). The interaction of these molecules (es.: selectin) with their ligands (non completely discovered) is characteristic of specific stages, but may also regulate the successive steps (integrin activation). In periodontal infections, PMNs of gingival tissue migrate towards bacteria of dental plaque along a chemotactic gradient of specific factors (ICAM-1, IL-8) produced by cells of the junctional epithelium. Such gradient is essential to drive PMNs through molecular traffic. Among the mechanisms used by PMNs to kill bacteria, the importance of nitric oxide (NO) production has been recently pointed out.