The nationwide unavailability of certain prescription medications has posed a potential patient safety problem, as these shortages have been increasingly common over the past few years. This study shows clear evidence that drug shortages can result in patient harm. In 2009, a shortage of mechlorethamine (a standard component of chemotherapy regimens for childhood leukemia) forced oncologists to treat patients with an alternative agent, cyclophosphamide (which was thought to be equally effective). This article demonstrates that children who received cyclophosphamide clearly had a higher rate of treatment failure, resulting in the need for further chemotherapy and bone marrow transplantation. This finding adds to other recent studies documenting clinical consequences directly related to drug shortages.