The cattle pathogen Anaplasma marginale (Rickettsiales: Anaplasmataceae) establishes persistent infections in cattle and tick hosts. In ticks A. marginale first infects gut cells, followed by infection of salivary glands, the site of transmission. Many geographic isolates of A. marginale are maintained in nature in individual hosts by a phenomenon of infection/exclusion. These isolates vary in genotype, antigenic composition and infectivity for ticks. Six major surface proteins (MSPs) are conserved on A. marginale from ticks or cattle. MSP1a, encoded by the single-copy gene msp1α, is differentially expressed in tick and bovine cells. Msp1α is a stable genetic marker for isolate identification and the varying numbers of repeats result in differences in the molecular weight. The tandem repeats are functionally important and contain adhesion molecules, neutralization sensitive and B-cell epitopes. The adhesive properties of the MSP1a repeats, influenced by protein conformation, structure and glycosylation, determine the ability of A. marginale isolates to infect ticks. Sequence variation among the repeats of A. marginale isolates may have resulted from evolutionary pressures exerted by ligand-receptor and host-parasite interactions. MSP2, derived from a multi-gene family, undergoes antigenic variation and contributes to the ability of A. marginale to maintain persistent infections in ticks and cattle. Although the function of the single copy gene, msp4, is unknown, it has been used to define phylogeographic relationships among A. marginale isolates. Infection and development of A. marginale in cattle and tick cells differs and appears to be mediated by several surface proteins encoded from the pathogen’s small genome.