Type II secretion (T2S) is one of six systems that can occur in Gram-negative bacteria for the purpose of secreting proteins into the extracellular milieu and/or into host cells. This chapter will describe the T2S system of Legionella pneumophila. Topics to be covered include the genetic basis of T2S in L. pneumophila, the numbers (>25), types, and novelties of Legionella proteins that are secreted via T2S, and the many ways in which T2S and its substrates promote L. pneumophila physiology, ecology, and virulence. Within the aquatic environment, T2S plays a major role in L. pneumophila intracellular infection of multiple types of (Acanthamoeba, Hartmannella, and Naegleria) amoebae. Within the mammalian host, T2S promotes bacterial persistence in lungs, intracellular infection of both macrophages and epithelial cells, and a dampening of the host innate immune response. In this context, T2S may represent a potential target for both industrial and biomedical application.