It has been nearly two decades since the discovery of Bartonella as an agent of bacillary angiomatosis in AIDS patients and persistent bacteremia and 'nonculturable' endocarditis in homeless people. Since that time, the number of Bartonella species identified has increased from one to 24, and 10 of these bacteria are associated with human disease. Although Bartonella is the only genus that infects human erythrocytes and triggers pathological angiogenesis in the vascular bed, the group remains understudied compared with most other bacterial pathogens. Numerous questions regarding Bartonella's molecular pathogenesis and epidemiology remain unanswered. Virtually every mammal harbors one or more Bartonella species and their transmission typically involves a hematophagous arthropod vector. However, many details regarding epidemiology and the public health threat imposed by these animal reservoirs is unclear. A handful of studies have shown that bartonellae are highly-adapted pathogens whose parasitic strategy has evolved to cause persistent infections of the host. To this end, virulence attributes of Bartonella include the subversion of host cells with effector molecules delivered via a type IV secretion system, induction of pathological angiogenesis through various means, including inhibition of apoptosis and activation of hypoxia-inducing factor 1, use of afimbrial adhesins that are orthologs of Yersinia adhesin A, incorporation of lipopolysaccharides with low endotoxic potency in the outer membrane, and several other virulence factors that help Bartonella infect and persist in erythrocytes and endothelial cells of the host circulatory system.