Numerous advances have been made in the management of infection in HSCT recipients. With increasing knowledge the authors are able to prevent several serious infections from occurring, and reduce the severity of infections once they occur. Despite these advances, several previously unrecognized pathogens have emerged and pose risks to this population. Ongoing surveillance and reporting of atypical infections are warranted. Transplant and infectious disease clinicians alike must be vigilant to the shifts in infectious syndromes as a consequence of various prophylaxis and preemptive strategies, and be ready to modify empiric strategies to meet the changing microbiologic milieu. As we increase our understanding of the HSCT process, and use the immune system rather than relying on high-dose chemotherapy, the authors are likely to reduce toxicities and improve patient outcomes.