Chryseobacterium gleum is a lactose nonfermenting Gram-negative bacillus (NFGNB) found in soil, plants, and some water sources but rarely implicated as a human pathogen. Its scarcity in the medical literature and resistance to numerous broad-spectrum antibiotics such as carbapenems, cephalosporins, and beta-lactam/lactamase inhibitors pose a diagnostic and therapeutic challenge. We present the first reported case, to the best of our knowledge, of sepsis from central line-associated blood stream infection from Chryseobacterium gleum in the United States.