INTRODUCTION: The management of patients with Polycythemia Vera (PV) traditionally includes low-dose aspirin, phlebotomy, and cytoreductive therapy for high-risk individuals. Recent evidence suggests that cytoreductive treatment may be warranted for patients with additional risk factors beyond the traditional criteria of a history of thrombosis and age over 60 years. Introducing new therapeutic agents, including ropeginterferon alfa-2b and ruxolitinib, enables a more personalized treatment approach tailored to individual patient characteristics. CASE REPORT: This report presents three complex clinical scenarios involving patients with PV who required cytoreductive therapy, which were discussed by a multidisciplinary advisory board. Each case is accompanied by a concise literature review and recommendations from non-hematologist specialists on managing adverse events associated with cytoreductive treatment. A multidisciplinary expert panel has identified three conceptual pathways to guide clinicians in selecting cytoreductive therapies and managing their associated complications. CONCLUSION: The advent of new criteria for starting cytoreduction and the approval of novel drugs for PV has increased the complexity of selecting appropriate cytoreductive therapies. A multidisciplinary approach is increasingly essential to ensure personalized care that maximizes tolerability and minimizes adverse events, particularly given the often chronic nature of the treatment.