INTRODUCTION: The use of herbal and dietary supplements (HDS) has been on a rise in the United States in the last couple of decades with roughly one half of the population consuming it. Artemisinin is found in the leaves of Artemisia annua and has been in use for a long time for its medicinal purposes. It is also a key ingredient in HDS and is generally considered safe and effective with no major side effects but very rarely, may lead to liver injury. Due to the HDS being unregulated, its increased use has led to an increase in adverse effects with hepatic injury being the most notable one. Here we present a case of HDS causing severe hepatic injury. CASE DESCRIPTION/METHODS: A 63-year-old female with a past medical history of generalized anxiety disorder and recurrent major depression, and with a recent history of over the counter supplement Microb-Clear consumption, presented with pruritus and generalized rash, of one week duration, associated with malaise, anorexia, intermittent nausea, yellow discoloration of the skin, dark urine and light stools. Her physical examination was significant for jaundice and diffuse maculopapular rash. Laboratory investigations revealed direct hyperbilirubinemia (7.3 mg/dl) with a cholestatic pattern of liver injury, with an upward trend in direct bilirubin and alkaline phosphatase noticed during the treatment course. The patient improved following discontinuation of the over the counter supplement, leading to a diagnosis of exclusion of HDS induced liver injury. DISCUSSION: The current regulations regarding supplements are inadequate and irrational. The general perception about safety and easy availability without the requirement of a medical prescription is one of the major causes of their misuse. They have unpredictable pharmacokinetics and pharmacodynamics as well as unknown drug interactions, increasing the probability of toxicity. As with our patient, discontinuing the supplements caused rapid symptomatic relief with improvement in liver function, which points towards a causal relationship between consumption of artemisinin-containing supplements and hepatic injury. The mechanism of the liver injury caused by artemisinin is still unknown. Further studies are required to study the relationship between HDS consumption and hepatic injury. A high index of suspicion is required to identify and minimize such adverse reactions in the future.