Coxiella burnetii is a widespread zoonotic bacterial pathogen that causes human Q fever. In vivo, Coxiella displays a tropism for mononuclear phagocytes where it participates in biogenesis of a lysosome-like replication compartment to conduct its obligate intracellular lifestyle. Coxiella actively regulates multiple events during infection, presumably via proteins with effector functions that are delivered to the host cytosol by a Dot/Icm type IV secretion system. Because the organism is currently refractory to genetic manipulation, Coxiella Dot/Icm substrates have been identified using bioinformatics and Legionella pneumophila as a surrogate type IV delivery system. Functional characterization of the biological activity of these effector proteins will dramatically aid our ability to model Coxiella-host cell interactions.