Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for patients with myelofibrosis. Because of inherent risk of the procedure, optimal timing in the course of the disease is crucial in order to balance risk and benefit. Besides optimal timing, reducing spleen size—a hallmark of the disease—is needed to ensure timely and sufficient engraftment after HSCT. Disease- and transplant-specific risk scores have been developed to predict the outcome of myelofibrosis with (MTSS) and without transplantation (DIPSS, MIPSS, and MYSEC), and current recommendation is to offer HSCT in primary or secondary myelofibrosis patients up to 70 years of age with intermediate-2 or high-risk DIPSS or MYSEC score or high risk according to MIPSS70 and a low or intermediate risk according to MTSS. Regarding the spleen size, the current European recommendation is for patients with splenomegaly greater than 5 cm below the lower costal margin or splenomegaly-related symptoms to receive a spleen-directed treatment, ideally with JAK-inhibitor and in case of resistance to use second-generation JAK inhibitor or spleen irradiation close to the transplant or splenectomy.