Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.