Introduction: Myelofibrosis is a complex heterogeneous disease which continues to challenge the treating clinician. Ruxolitinib, the first JAK inhibitor approved, delivers a reduction in splenomegaly and disease-related symptoms, and likely prolongs survival. JAK inhibitors are being trialled in combination and appear to alleviate anaemia, thrombocytopenia or deepen response. However, a number of patients may not gain benefit, lose their response or are not able to tolerate ruxolitinib. Areas covered: There remains a need for alternative agents in myelofibrosis patients in whom JAK inhibitors have failed or are not tolerable. We discuss the different therapeutic options currently available and explore pomalidomide as a therapeutic option in anaemic, and/or thrombocytopenic patients with or without splenomegaly. Expert opinion: The responses documented in clinical trials suggest pomalidomide efficacy might be variable with a limited benefit in improving constitutional symptom burden or reversing the disease process. However, a number of phase-II trials have demonstrated pomalidomide is a safe and efficacious option in managing splenomegaly, reducing transfusion requirements and in a minority improving platelet number. As we discuss, pomalidomide, which is currently approved for use in multiple myeloma, is a potential alternative in the challenging myelofibrosis patient where thrombocytopenia and anaemia exist.