Gram-negative bacteremia has been associated with severe sepsis, although the exact mechanism and pathophysiological differences among bacterial species are not well understood. In the previous issue of Critical Care, Abe and colleagues report results of a retrospective study that show a significantly higher incidence of Gram-negative bacteremia among adult intensive care unit patients with septic shock than in those with sepsis or severe sepsis. In this study, C-reactive protein and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These observations suggest a distinct immunopathophysiologic behavior of sepsis in patients with Gram-negative bacteremia that may influence clinical outcomes. Future research exploring new biomarkers and danger signals and further characterizing differences in the virulence mechanisms between Gram-negative and Gram-positive bacteria appears promising and could lead to new therapeutics and to improved clinical outcomes.