In May–June 2011, an unprecedented outbreak of hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing E. coli (STEC) O104:H4 affected >800 adults, in whom this disorder is usually rarely seen. Over 90 children were also affected in the largest STEC-associated HUS outbreak in children to date. Despite high patient numbers and chronic staff shortages in pediatric institutions, almost all patients were treated locally, mainly because of maximally increased staff input. Epidemiologic features were characterized by relatively high age at presentation, possibly related to the isolated etiologic agent, raw bean sprouts. Fortunately, in children, other clinical features, including neurological complications, dialysis requirement, and short-term outcome, were comparable to previous historical series. Only one child died, compared to 35 adults. Differences in treatment recommendations and approaches between adults and children were noted. Treatment with eculizumab was available, but handled more restrictively in children. Despite treatment differences, children and adult clinical outcomes were comparable, pending a final analysis. In summary the STEC O104:H4 HUS outbreak was challenging for pediatric resources but clinical presentation and complications were comparable to previous experience. Acute outbreak onset made structured approaches to treatments impossible, however, ongoing analysis may provide evidence for improving care of children with STEC HUS.