 Stem cells are usually thought of as possible treatments for diseases like spinal cord injuries or type 1 diabetes in which cells need to be replaced. But increasing evidence suggests they may be able to help with sepsis, a life-threatening complication of infection. Sepsis is one of the most deadly and expensive syndromes, killing a quarter of a million people and incurring $20 billion in hospital costs every year in the United States alone. Classically, sepsis has been thought of as a problem of an overactive immune system. As immune cells respond to infection, they unleash a torrent of inflammatory cytokines, or what's called a cytokine storm, which can lead to organ failure. But recently, doctors have discovered that sepsis is more complicated and if someone survives this early hyper-inflammatory stage, they are still at risk of succumbing later when the syndrome switches over to being immune-suppressive. Currently, there are no treatments beyond antibiotics, which need to be given early to be fully effective. Multipotent stromal or connective tissue cells known as mesenchymal stem cells may be ideally suited to fighting sepsis. Preclinical studies have found that they can strengthen the immune response to pathogens while limiting host damage and boosting tissue repair. And because the cells have few antigen-presenting molecules on their surface, they are less likely to be rejected. This means that they can be taken from a donor, stored and transplanted into another patient, much like we do with blood products today. In animal models of sepsis, researchers have found that stem cells are protective and operate through a variety of mechanisms. The cells reduce bacterial growth with antimicrobial peptides and activate macrophages to phagocytose and kill pathogens. At the same time, stem cells keep the immune response in check by promoting T-regulatory cells and producing the right mix of cytokines and chemokines to keep neutrophils from spreading into healthy tissues. The cells also pass mitochondria onto the epithelium to reduce injury in the lung. These studies demonstrate the potential for stem cells to radically improve sepsis treatment, but substantial hurdles remain. Clinical trials are mostly just getting started, and those in progress or completed for other diseases have struggled to replicate some of the animal results, indicating the need for caution. Complicating things is the fact that no one marker can identify mesenchymal stem cells, and they're a heterogeneous population anyway. We don't yet know which sources may be better at fighting sepsis or what the best doses are and when to give them. Finally, while the cells appear mostly safe, there are still concerns about infusional toxicity and whether they can contribute to cancer. More work is needed to investigate what goes on in the body during sepsis and whether stem cells will ultimately be an effective treatment for one or more subtypes of the condition.