Salmonella enterica engages host cells in a complex two-way biochemical interaction that results in a variety of responses from both the bacteria and the host cell. Central to this interaction is the function of a type III protein secretion system that delivers effector proteins into the host cell. During the past year we have seen major advances in our knowledge of both the bacterial determinants and the host-signal transduction pathways involved in these interactions. A coherent picture of the mechanisms by which Salmonella engages the host cell is now beginning to emerge.