spp., especially and , are leading bacterial foodborne pathogens worldwide. In the United States, an estimated 0.8 million cases of campylobacteriosis occur annually, mostly involving Campylobacteriosis is generally self-limiting, but in severe cases, treatment with antibiotics may be mandated. The increasing incidence of fluoroquinolone resistance in has rendered macrolides such as erythromycin and azithromycin the drugs of choice for human campylobacteriosis. The prevalence of macrolide resistance in remains low, but macrolide resistance can be common in Substitutions in the 23S rRNA gene, specifically A2075G, and less frequently A2074C/G, remain the most common mechanism for high-level resistance to macrolides. In , resistance mediated by such substitutions is accompanied by a reduced ability to colonize chickens and other fitness costs, potentially contributing to the low incidence of macrolide resistance. Interestingly, similar fitness impacts have not been noted in Also noteworthy is a novel mechanism first reported in 2014 for a isolate from China and mediated by (B) harbored on multidrug resistance genomic islands. The incidence of (B) appears to reflect clonal expansion of certain strains, and whole-genome sequencing has been critical to the elucidation of (B)-associated macrolide resistance in spp. With the exception of one report from Spain, (B)-mediated macrolide resistance has been restricted to spp., mostly , of animal and human origin from China. If (B)-mediated macrolide resistance does not confer fitness costs in , the range of this gene may expand in , threatening to compromise treatment effectiveness for severe campylobacteriosis cases.