Hematopoietic stem cell transplantation (SCT) is a therapeutic option for patients with bone marrow failure, certain malignancies and inborn errors of metabolism. Complications requiring intensive care are frequent, and intensivists need to be familiar with the transplantation process and the disorders that are unique to these patients. The transplant process involves the use of high dose chemotherapy or radiation, followed by intravenous infusion of stem cells matched with the recipient at the human leukocyte antigen (HLA) loci. Full recovery of a normal immune system can take a year or more, so following transplantation, patients are exquisitely susceptible to infections. Moreover, complications such as graft versus host disease, idiopathic pneumonia syndrome, sinusoidal obstruction syndrome and transplant associated thrombotic microangiopathy are common in the first hundred days after stem cell infusion. Respiratory failure is a common presentation necessitating intensive care admission and may be due to infectious or non-infectious causes. Mechanical ventilation may be needed along with broad spectrum anti-microbial coverage; corticosteroids are commonly used if graft versus host disease is present. Acute graft versus host disease is most frequent in children receiving grafts from unrelated donors and results in significant morbidity. Increased immunosuppression is the cornerstone of therapy for graft versus host disease, and protection of the children from infection is essential to survival. Sinusoidal obstruction syndrome and transplant associated thrombotic microangiopathy may lead to multiple organ failure with limited therapeutic options, but both disorders can resolve with good supportive care during the period of organ failure. Outcomes for patients who develop multiple organ failure following SCT remain poor despite aggressive supportive care, however, children with failure of a single organ can do well. Integrated multi-disciplinary care between intensivists and transplant physicians, and other specialists such as nephrologists and pulmonologists leads to improved outcomes.