Klebsiella pneumoniae-associated liver abscesses have distinct clinical and epidemiologic features. We report the unusual case of an American patient with a K. pneumoniae-associated liver abscess and septic spread to other organs. We additionally present a comprehensive review of K. pneumoniae-associated liver abscess syndromes in adults. We identified three distinct K. pneumoniae liver abscess syndromes: the polymicrobial liver abscess, the monomicrobial cryptogenic noninvasive liver abscess, and the monomicrobial cryptogenic invasive K. pneumoniae-associated liver abscess (CIKPLA) syndromes, with distinct clinical, epidemiologic and outcome features. CIKPLA syndrome typically affects diabetic patients, mainly in Southeast Asia, and is complicated by septic spread to other organs. The community-acquired, monomicrobial, K. pneumoniae-associated liver abscess syndromes that typically occur in the USA are mainly noninvasive and affect Asian or Hispanic persons. However, this report provides an alert that CIKPLA syndrome can occur in North America, and physicians need to be aware of it.