The body relies for protection on an effective inflammatory response. To sustain an armoury of inflammatory cells in a state of permanent activation would be impossible and a system whereby such cells can be rapidly activated is, therefore, employed. Upon transition from the resting to activated state inflammatory cells perform multiple defensive functions and are then removed, limiting the duration of inflammation. Neutrophils are the major circulating inflammatory cells but macrophages exert a more powerful regulatory effect. If the inflammatory response is inadequate there is a risk of overwhelming sepsis. By contrast, an unregulated response can lead to systemic inflammation and consequent multiple organ damage. This review focuses on the mechanisms whereby inflammatory cells are activated, how the regulatory system may misfunction and how it may in the future be manipulated to therapeutic advantage.