Ralstonia spp. are non-fermenting aerobic gram-negative rods found in humid environments, whose role as opportunistic human pathogens has lately been recognized. Ralstonia mannitolilytica is one of the three members of the Ralstonia genus (together with Ralstonia pickettii and Ralstonia insidiosa). Bone infections by Ralstonia spp. are very rare. We report a case of femoral osteomyelitis caused by R. mannitolilytica. Among literature search, only eight cases of bone infection due to the Ralstonia genus have been described, in all of which the causative agent was identified as R. pickettii. To our knowledge, this is the first reported case of osteomyelitis attributed to R. mannitolilytica. Despite its low virulence, Ralstonia has specific characteristics that promote its spread and shows high antibiotic resistance, partly due to its ability to create a biofilm. Identification of Ralstonia spp. poses unique difficulties as the distinction between the species of the genus is not straightforward. Additionally, the bacteria may be misidentified as other closely related species. Recent data suggests that modern spectrometry and gene sequencing techniques are essential to avoid these pitfalls. Susceptibility data about the genus is limited and based on a small number of case reports, therefore there is no standardized antibiotic susceptibility testing and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints exist. The report aims is to provide useful information on the antibiotic selection and treatment suggestions to be followed for bone infections caused by the Ralstonia genus, along with a review on the literature of this emerging opportunistic pathogen.