Cytokines orchestrate the complex network of cellular interactions that regulate effector cell functions of natural and immune resistance. Although T cells, natural killer (NK) cells and monocytes/macrophages are the main producers of cytokines, a number of reports in the last few years have demonstrated that polymorphonuclear neutrophils (PMN) also have the ability to synthesize and release immunoregulatory cytokines. Here, Marco Cassatella describes novel facets of the regulation of cytokine production by PMN that highlight the involvement of of PMN in cell-cytokine crosstalk.