Portal vein thrombosis (PVT) is characterized by the formation of a thrombus (blood clot) within the portal vein system, including main portal vein and its intrahepatic portal vein branches, and may extend to the superior mesenteric vein or splenic vein. The emergence of PVT is linked to diverse risk factors, encompassing liver conditions with cirrhosis, abdominal infections, previous abdominal surgeries, malignancies, inherited or acquired thrombophilias, and systemic hypercoagulable conditions. Recent studies revealed a possible connection between the occurrence of PVT and either contracting corona virus disease 2019 (COVID-19) or receiving a COVID-19 vaccination. Current treatment strategies were primarily based on symptom management, extent, and progression of thrombosis, but their efficacy was inconsistent and suboptimal. Untimely or inadequate treatment can lead to the progression of the thrombus and increase the risk of complications, such as portal hypertension, variceal bleeding, and hepatic decompensation, posing a significant risk to the patient’s life. Thus, early and appropriate initiation of pharmacologic and interventional treatments, as well as more aggressive strategies, is crucial for the management and prevention of PVT progression and recurrence. This review focuses on the literature on the recent advancements in the treatment of PVT using various therapeutic modalities, including anticoagulant therapy, thrombolysis, thrombectomy, interventional therapy and liver transplant in cirrhotic patients. In addition, we discuss pearls and pitfalls of these strategies for PVT, highlighting recent progress, identifying knowledge gaps, and proposing avenues towards precision management.