The lack of a consensus definition of ruxolitinib failure, combined with a growing number of treatment options, adds to the challenges facing clinicians (hematologists, hematologist-oncologists, and advanced practice providers) who treat patients with primary myelofibrosis. These include expeditiously recognizing intolerance or treatment resistance with ruxolitinib and then selecting and transitioning patients to the most appropriate next therapy for each patient. This program provides data-driven expert guidance to help clinicians promptly identify ruxolitinib failure, select next-line therapy based on patient-specific clinical needs and preferences, and apply best practices for safely transitioning from ruxolitinib to next therapy and management of AEs. It also provides recommendations on engaging patients to share in treatment decisions that address their symptoms and reflect their preferences regarding their quality of life.