Purpose of reviewHyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients. Growing evidence suggests hyperammonemia syndrome is associated with systemic infections caused by urease-producing organisms, namely Ureaplasma spp., an organism unable to grow with routine culturing techniques. This review will summarize the epidemiology and clinical manifestations of hyperammonemia syndrome, as well as diagnostic and management strategies once hyperammonemia syndrome is suspected.Recent findingsHyperammonemia syndrome is being described in increasing frequency in the solid organ transplant population. Morbidity and mortality, even with treatment, is high once hyperammonemia syndrome occurs. Surveillance studies indicate the prevalence of lung donor colonization with Ureaplasma spp. is high, suggesting screening and treatment may be of benefit. Antibiotic resistance is common, and rapid diagnostics can facilitate appropriate antimicrobial therapy in the peri-transplant period.SummaryHyperammonemia syndrome is most commonly seen in lung transplant recipients and has a high mortality rate once it occurs. Screening for Ureaplasma spp. should be considered in all lung transplant donors.