Cytomegalovirus (CMV) remains a significant contributor to morbidity and death after pediatric solid and stem cell transplantation. Decisions regarding prevention and treatment often lack pediatric-specific data to drive decision making. We present here a case-based discussion around some of these specific topics and focus on approaches to CMV prevention, post-CMV secondary prophylaxis options, and identification and treatment of resistant CMV infection, including emerging antiviral agents and the use of cytotoxic CMV-specific T-cells, in the setting of pediatric hematopoietic stem cell transplantation.