Methylobacterium mesophilicum is a methylotrophic, pink pigmented, gram-negative rod that was initially isolated from environmental sources that is being increasingly reported as a cause of opportunistic infections in immunocompromised hosts. We present the case of an immunocompromised woman who developed a central catheter infection with M. mesophilicum and review the other 29 cases reported in the literature, noting that it is frequently resistant to beta-lactam agents but is generally susceptible to aminoglycosides and quinolones.