One century after the first description of rickettsiae as human pathogens, the rickettsiosis remained poorly understood diseases. These microorganisms are indeed characterized by a strictly intracellular location which has, for long, prohibited their detailed study. Within the last ten years, the completion of the genome sequences of several strains allowed gaining a better knowledge about the molecular mechanisms involved in rickettsia pathogenicity. Here, we summarized available data concerning the critical steps of rickettsia-host cell interactions that should contribute to tissue injury and diseases, that is, adhesion, phagosomal escape, motility, and intracellular survival of the bacteria.