Myelofibrosis (MF) is a disorder characterized by the proliferation of myeloid precursors, commonly due to overactive JAK signaling. The discovery of the JAK2V617Fmutation and subsequent development of JAK inhibitors (JAKi) results in reduced spleen size, improved symptom, and enhanced survival in MF patients. However, there are unmet needs of additional novel targeted therapies for this incurable disease due to the limited utility of first-generation JAKis, which are associated with dose-limiting cytopenia and disease recurrence. New targeted treatment strategies for MF are on the horizon. We are here to discuss the latest clinical research findings presented in the 2022 ASH Annual Meeting.