Myelofibrosis (MF) is a chronic malignancy of the blood-forming system caused by hyperactivation of JAK2/STAT signaling pathway. Small-molecule inhibitors of JAK2 can variably ameliorate MF-related symptoms caused by chronic inflammation and hepatosplenomegaly. Anemia is a significant problem and adverse prognostic factor in over a third of MF patients and is often worsened by JAK2 inhibitors. The JAK1/2 inhibitor momelotinib unexpectedly resulted in reduction of anemia in MF patients during Phase I/II trials. Current Phase III trials will be the basis for seeking regulatory approval of momelotinib during 2017. Studies to determine how momelotinib improves anemia are underway, potentially leading to expanded momelotinib use and/or development of other targeted therapies for treating anemia in MF and related diseases.