While the relative contributions that ischemia, TLR-4-mediated pathways, apoptosis, and other subcellular processes have towards overall organ dysfunction are currently unclear, the abundance of research in the area has shed a significant amount of light on the basic mechanisms that drive septic AKI. Perhaps the most important finding is that therapeutic approaches targeted at a single mediator for all patients may not succeed given the protean nature of the disease. Indeed, targeted inhibition of cytokines such as TNF-α and IL-1 as well as TLR antagonists have failed to show consistent and significant clinical benefit, most likely because only certain subsets of septic patients fit an immunologic profile that would benefit from those therapies. An important next step in sepsis research should be to identify immunologic markers in patients that can help tailor specific therapies for patients based on where they lie along the immunologic spectrum.