Chemokines have a clearly defined role in mobilizing the recruitment of leukocytes to both healthy and inflamed tissues. This review details work from our and other laboratories, indicating that beta-chemokines may play important roles (i) in driving the terminal differentiation of mast cell precursors in mucosal tissues and (ii) in providing priming or costimulatory signals required for mast cell activation, leading to an antigen-driven inflammatory response. These data stem from in vivo, ex vivo, and in vitro studies. Data are also presented that suggest that Fc epsilon RI:chemokine receptor cross talk may involve spatiotemporal dynamics that may control the strength and nature of the complex activating signals controlling mast cell effector function.