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Hematopoietic stem cell (HSC) transplants are widely used to treat patients with cancer and other disorders of the blood and immune system. The isolation of human HSC offers the promise for obtaining a remarkable variety of new therapeutics. Thus, an effort to analyze and assess the safety of these cells is extremely important. As with blood transfusion, microbial infections have been transmitted by HSC transplantation. Due to the inability to sterilize HSC and the immunodeficient nature of their recipients, the risk of infectious disease transmission remains a major concern. Assessing HSC safety requires careful monitoring of their collection, manipulation, and distribution. This review describes the pathogens that are recovered from HSC products, and the approaches available for detecting microbial contamination in HSC products prior to transplant.