Chronic liver disease (CLD) is an under-recognized epidemic that continues to increase in prevalence and is a major health concern. Silymarin, the active compound of Silybum maria-num (Milk thistle), has historically been used in CLD. A sig-nificant barrier to silymarin use is its poor bioavailability. Attempts at improving the bioavailability of silymarin have led to a better understanding of formulation methods, phar-macokinetics, dosing, and associated drug interactions. Clin-ically, silymarin exerts its hepatoprotective effects through antioxidative, antifibrotic, anti-inflammatory, antitoxin, and anticancerous mechanisms of actions. Despite the use of si-lymarin being extensively studied in alcoholic liver disease, metabolic-associated fatty liver disease, viral hepatitis, and drug-induced liver injury, the overall efficacy of silymarin re-mains unclear and more research is warranted to better elu-cidate the role of silymarin in CLD, specifically regarding its anti-inflammatory effects. Here, we review the current bio-chemical and clinical evidence regarding silymarin in CLD.