There is growing global concern regarding the rise of antibiotic-resistant organisms. Many of these reports have focused on various Gram-positive and Gram-negative pathogens, with little attention to the genus Ureaplasma. Ureaplasma spp. are associated with numerous infectious diseases affecting pregnant women, neonates and the immunocompromised. Treatment options are extremely limited due to high levels of intrinsic resistance resulting from the unique physiology of these organisms and further restricted in cases of the developing fetus or neonate, often limiting therapeutic options to predominantly macrolides or rarely fluoroquinolones. The increasing presence of macrolide- and fluoroquinolone-resistant strains among neonatal infections may result in pan-drug resistance and potentially untreatable conditions. Here, we review the requirements for accurate measurement of antimicrobial susceptibility, provide a comprehensive review of the antimicrobial resistance (AMR) for Ureaplasma species in the literature and contextualize these results relative to some investigators' reliance on commercial kits that are not CLSI compliant when determining AMR. The dramatic variation in the resistance patterns and impact of high levels of AMR amongst neonatal populations suggests the need for continued surveillance. Commercial kits represent an excellent tool for initial antibiotic susceptibility determination and screening. However, AMR reporting must utilize internationally standardized methods, as high-titre samples, or Mycoplasma hominis-contaminated samples routinely give false AMR results. Furthermore, there is a requirement for future reports to determine the underlying AMR mechanisms and determine whether expanding AMR is due to spontaneous mutation, transmission of resistance genes on mobile elements or selection and expansion of resistant clones.