Peanuts (A. hypogaea) are an economically important crop, a source of food allergies and a member of the South American genus Arachis. The eighty species of genus Arachis have been divided into nine sections. The largest, section Arachis, has been further subdivided into three genome groups. The current intuitive understanding of the evolutionary relationships among Arachis is based on morphological, geographic and cytogenetic data, but a comprehensive phylogenetic study for the genus is lacking. A total of 48 species representing all nine sections were used to reconstruct a phylogeny based on sequence information from plastid trnT-trnF and nuclear ITS genomic regions. Phylogenetic analysis resolved section Extranervosae at the base, followed by sections Triseminatae and Caulorrhizae. Two major terminal lineages were recovered. One is comprised of sections Erectoides, Heteranthae, Procumbentes, Rhizomatosae, and Trierectoides, referred to here as group erectoides. The other is comprised of two major clades, arachis I (B genome, D genome, and aneuploid species) and arachis II (A genome species). The phylogenetic trees show that sequence data partially agrees with the relationships described in the monograph; however, some further investigation is necessary to clarify relationships within and among species of the two terminal lineages. In addition, the major allergen Ara h 2 from 12 wild species from across the genus was analyzed for mutations that could potentially produce a hypoallergenic ortholog. It was found that the evolution of the allergen mostly reflected the species phylogenies based on ITS and combined. The majority of substitutions and length variations were concentrated in the loop connecting helices H2 and H3. Section Arachis species tended to have larger H2-H3 loops, while those from other sections had shorter loops. The immunodominant epitopes #6 and #7, located within this loop, tended to contain mutations or were truncated among species outside of section Arachis. Dot immunoblots showed reduced IgE-binding to peptides representing portions of the H2-H3 loop from A. guarantica and A. triseminata. Orthologs from wild species have demonstrated that they could potentially contain variations of the allergen Ara h 2 that could be utilized to develop a safer peanut cultivar.