INTRODUCTION: The percentage of drug-induced liver injury due to the use of herbal supplements has exponentially increased over the last decade from 7% to about 20%. Liver injury attributed to supplement use is associated with more deaths than cases attributed to anabolic steroid use or even allopathic medications. CASE DESCRIPTION/METHODS: 53-year-old female presented with jaundice, pruritus, fatigue, clay-colored stools and dark-colored urine for 4 days. She reported taking an herbal supplement called cascara sagrada for constipation over an 8-week period. On physical examination she appeared jaundiced, abdomen was non-tender, non-distended, and there was no hepatomegaly. Laboratory tests were significant for total bilirubin 8.2 mg/dL, direct bilirubin 5.5 mg/dL, ALP 459 U/L, GGT 733 U/L, AST 1274 U/L, ALT 1711 U/L, INR 0.97, ferritin 1409 ng/ml, transferrin saturation 59%, viral hepatitis antigens and antibodies were negative and an autoimmune panel was unremarkable. Liver ultrasound revealed coarse echotexture with no hepatomegaly and no biliary dilatation. Patient was discharged with close follow up. Five days after discharge, total bilirubin was 19 mg/dL with worsening symptoms necessitating re-admission. Further workup with liver biopsy showed marked portal and lobular chronic inflammatory infiltrate and focal bile duct injury and cholestasis; iron stain showed minimal Kupffer cell iron deposition but no hepatocellular deposition. Patient improved clinically and biochemically after discontinuation of cascara sagrada, with normalization of liver function tests after 3 months of the initial presentation. DISCUSSION: Cascara Sagrada is a herbal medication used for short term treatment of constipation, generally well tolerated but is known to cause liver injury when used in higher doses than recommended. Anthraquinone derivatives are the active laxative components; promoting peristalsis and inhibiting reabsorption of water and electrolytes. Cascara is slightly absorbed, and typical recommended courses are for less than 7 days. The mechanism of liver injury is not well understood but it has been hypothesized that it is mediated by the direct toxicity of anthraquinone derivatives. Liver injury can present with a pattern of serum enzyme elevation that can be either hepatocellular or cholestatic and ranges in severity from mild transaminase elevation to severe hepatitis with associated portal hypertension and ascites. Nevertheless, injury is usually self-limited and typically reversible upon discontinuation.