Large regenerative nodules are benign liver lesions that are frequently seen in Budd-Chiari syndrome and less commonly in other vascular disorders of the liver or systemic conditions such as autoimmune disease, myeloproliferative disorders, and lymphoproliferative disorders. They are usually multiple, with a typical diameter of 0.5-4 cm. At pathologic analysis, large regenerative nodules are well-circumscribed, round lesions that may distort the contour of the liver. Only a minority of these nodules are detected at cross-sectional imaging. At multiphasic helical computed tomography, large regenerative nodules are markedly and homogeneously hyperattenuating on arterial dominant phase images and remain slightly hyperattenuating on portal venous phase images. Large regenerative nodules are bright on T1-weighted magnetic resonance images and show the same enhancement characteristics after intravenous bolus administration of gadolinium contrast material. They are predominantly isointense or hypointense relative to the liver on T2-weighted images. There is no evidence that large regenerative nodules degenerate into malignancy. If these nodules are misdiagnosed as multifocal hepatocellular carcinoma, patients might be denied transplantation or offered inappropriately aggressive therapy such as transcatheter arterial chemoembolization. Understanding the clinical setting and imaging appearance of large regenerative nodules can help avoid misdiagnosis as other hypervascular masses.