Graft-versus-host disease (GvHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation. Only half of patients with severe acute GvHD respond to first-line treatment with corticosteroids and, for several decades, there was no optimal second-line treatment for patients with corticosteroid-refractory acute GvHD. Ruxolitinib was recently approved for the treatment of corticosteroid-refractory acute GvHD in adult and pediatric patients 12 years and older. Thus, it is important to define the patient population which would now be considered as refractory to ruxolitinib versus ruxolitinib-dependent. Here, we propose to define ruxolitinib-refractory acute GvHD as disease that shows (i) progression of GvHD compared to baseline after at least 5 to 10 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; (ii) lack of improvement in GvHD (PR or better) compared to baseline after at least 14 days of treatment with ruxolitinib; or (iii) loss of response, defined as objective worsening of GvHD determined by increase in stage, grade or new organ involvement at any time after initial improvement. GvHD manifestations that persist without improvement in patients who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib would serve as a clinical indication for additional treatment. In addition, absence of complete response or very good PR at day 28 after ruxolitinib could be considered as an eligibility criterion.