The chemical signals within neutrophils that control their behaviour are complex and these signals control the complex activity of neutrophils with precision. Failure of neutrophils to reform their antibacterial activity would lead to infection, while over-activity of neutrophils may lead to tissue damage and inflammatory disease. The identity of some of the intracellular signals is becoming clear and insights into the potential for interplay between them are being sought. Although it is well established that cytosolic free Ca(2+) plays a role, it is only recently that the importance of intracellular protease, calpain, and the 3-position phosphorylated phosphatidyl inositides is becoming recognised. In this review these three key signals are discussed as potential therapeutic targets for the modulation of neutrophil activity.