When faced with an invasion of microbes or non-infectious tissue damage, surrounding cells send for help. Leukocytes respond to these signals and infiltrate the injured tissue to help fight infection and cleanup damage. The idea that innate immune cells are mobilized early in the inflammatory response is not new. But with the advent of techniques to visualize immune cells in vivo in real time, together with novel genetic tools and models of inflammation, complex migratory patterns that are highly specific to the type of initiating inflammatory stimuli emerge. In this special issue of Trends in Immunology we commissioned a series of reviews that investigate how innate immune cells navigate their way to infected or injured tissues, together with the mechanisms that underlie inappropriate cellular migration in chronic inflammatory disease.Neutrophils are among the first and most numerous cell type to arrive at stressed tissues. Luster and colleagues (pp. 452–460) highlight how in vivo studies reveal that trafficking signals act at specific co-ordinates along the journey of a neutrophil from bone marrow to blood, to tissues and within tissues to the inflammatory site. These intricate control mechanisms are not only tailored to the type of inflammation but also differ during the course of inflammation–at least in a mouse model of arthritis. Luscinskas and colleagues (pp. 461–469) also discuss neutrophils but with focus on how these cells interact with blood vessels, as well as the cellular changes that underlie departure from the circulation and movement through tissues.Typically, monocytes are next to enlist their help at the inflammatory site, where they can differentiate to become dendritic cells or macrophages. On pp. 470–477 Ingersoll et al. tackle how monocytes home to inflamed tissue: a question complicated by the presence of two major circulating monocyte subsets in mice and humans. The authors describe how classical monocyte recruitment predominates during the intense inflammation that accompanies infection, whereas acute inflammation after heart injury also involves healing non-classical monocytes. Both monocytes subsets are recruited during chronic vessel inflammation in atherosclerosis, and in this context they seem damaging to the host.Weller and colleagues (pp. 478–485) describe how mast cells circulate in low numbers as committed progenitors and mature in tissues in response to local growth factors and cytokines. The authors highlight some of the challenges in the field of mast cell migration, and discuss recent progress in understanding the molecules that direct mast cells and their progenitors to the appropriate location in tissues.Natural killer (NK) cells actively seek out signs of tissue perturbation as they patrol lymphoid and non-lymphoid organs. They are further recruited to these sites in inflammatory conditions such as infection, autoimmunity, asthma and cancer. Walzer and Vivier (pp. 486–492) discuss how trafficking molecules, or so-called chemoattractants, specific for NK cell G protein-coupled receptors dictate the NK cell itinerary depending on the stage of cellular development and the type of inflammation. Although the individual roles of these chemoattractants in directing NK cells are becoming elucidated, how they interact and co-operate during an immune response is largely unknown.Hematopoietic stem and progenitor cells (HPSCs) mostly reside in bone marrow. But at any one time, a minor fraction flux between the bone marrow, blood, tissues and lymphatics. Mazo et al. (pp. 493–503) discuss the available approaches for studying this movement, and the underlying mechanisms that have emerged. Not only are HSPCs the source of innate immune cells, but inflammatory signals can increase HSPC ‘transit’ time in peripheral tissues, during which HSPCs might differentiate into innate immune cells to bolster local immune responses.A common theme throughout these reviews is whether or not new insights into how innate immune cells arrive at a site of inflammation will translate into novel approaches for anti-inflammatory therapy. With the realization of ever-more sophisticated processes for innate immune cell trafficking comes improved prospects for rational design of strategies to reduce inflammation in specific clinical conditions.We would like to thank the expert authors and reviewers who contributed to this themed issue of Trends in Immunology for their effort and opinion. We hope that you enjoy the result and welcome your feedback (immunology@cell.com).