Medicinal plants are rich sources of natural products, the principal constituents in herbal medicines, utilized for the treatment and prevention of diseases. High consumer expectations for health care, in the face of soaring cost of conventional pharmaceuticals, have popularized herbal medicines in different regions of the world. The consumption of these botanicals and their products has recently gained much impetus with the assumption that since these active principles in them are natural, they are, therefore, safe. Assertive as this idea could be, scrutinizing the perspectives on which it is premised is critical in minimizing probable risk on human health. Most plant parts are repositories of natural toxins, phytosteroids, and bioaccumulated toxicants, all of which are driven by natural processes. Besides intrinsic toxicity possessed by phytotoxins, some innocuous chemicals in medicinal plants can be biotransformed to toxic components. Some chemicals in medicinal plants that are of safety concerns include the endocrine-disrupting chemicals such as phytoestrogens, bisphenol A, and phthalates, among others. The persistent, bioaccumulative, and toxic metals have also been identified in medicinal plants. Some of these chemicals have been found to cause metabolic derangement and carcinogenicity. It is, therefore, imperative that linking natural products to safety should rather be empirical.