Directed movement along a concentration gradient of chemical attractants is essential for the survival of microbes and for the effectiveness of the immune system's phagocytic cells that pursue and engulf them. This directional motility (called chemotaxis) is governed by chemoattractants such as interleukin-8 (IL-8), C5a, and the formylated peptide N-formyl-Met-Leu-Phe (fMLP), which bind to receptors on the surface of cells. Chemoattractant receptors belong to the seven-transmembrane helix receptor family. After binding their chemoattractant ligands, these receptors become activated and transmit their signals to heterotrimeric G proteins (see the figure). The G protein complex dissociates into the α subunit and the βg subunits, which in turn bind and activate target enzymes such as phospholipase C, phosphoinositide 3-kinase (PI 3-kinase) or adenylyl cyclase. These enzymes generate intracellular messengers that initiate a cascade of events culminating in the biological response to the receptor signal. Five papers in this issue of Science (1-5) investigate how PI 3-kinase is involved in heptahelical receptor signaling and chemotaxis. Together they give us new insights into the intracellular machinery that chemoattractant receptors harness to produce their downstream effects.