Pyrrolizidine alkaloids (PAs) are a class of hepatotoxic compounds that are largely found in plants. "Zicao" is one of the most commonly-used Chinese herbal medicines from multiple sources, owing to its anti-inflammatory and wound healing effects. However, many studies have shown that this herb and its relative species contain hepatotoxic PAs. These PAs may cause hepatic sinusoidal obstruction syndrome following metabolic activation, and are therefore considered as potential toxic substances. Even though the toxicity of "Zicao" in clinical use has not been reported, the existence of PAs will undoubtedly post a threat for its safety in long-term use. It has now become the focus of many researchers to disclose and prevent its potential risk of intoxication. This review summarizes recent progress and key scientific evidence found in the research of pyrrolizidine alkaloids from "Zicao" and its relative species, including their metabolic toxicity. We comment on the need of future studies, such as providing a reference or guidance for safety evaluation of this medicinal herb in clinical practice.