Many bacterial pathogens can cause acute infections that are cleared with the onset of adaptive immunity, but a subset of these pathogens can establish persistent, and sometimes lifelong, infections. While bacteria that cause chronic infections are phylogenetically diverse, they share common features in their interactions with the host that enable a protracted period of colonization. This article will compare the persistence strategies of two chronic pathogens from the Proteobacteria, Brucella abortus and Salmonella enterica serovar Typhi, to consider how these two pathogens, which are very different at the genomic level, can utilize common strategies to evade immune clearance to cause chronic intracellular infections of the mononuclear phagocyte system.