Kluyvera is a relatively newly described genus in the family Enterobacteriaceae that infrequently causes infections in humans. The organism has been isolated from various clinical specimens, but its significance has not been clearly established. In fact, it has been regarded alternatively as saprophytic, opportunistic, or pathogenic. Since the redefinition of this genus in 1981, case reports of diverse clinical infections occurring under various host conditions have been published. Here we present a critical review of all Kluyvera infections reported in the literature, along with our experience involving 5 additional cases. Most patients received prompt antimicrobial treatment on the basis of susceptibility testing, and overall the clinical outcomes were good. Antimicrobial agents active against most Kluyvera strains include third-generation cephalosporins, fluoroquinolones, and aminoglycosides. In contrast, the resistance to ampicillin, extended-spectrum penicillins, and first- and second-generation cephalosporins is significant. Kluyvera is a potentially virulent pathogen that deserves aggressive treatment designed with an awareness of the organism's antimicrobial resistance patterns.