Ethnopharmacological Relevance: The genus Sambucus L. (Viburnaceae) consists of about 29 recognized species distributed in all regions of the world except the extremely cold and desert areas. Some species have been used as traditional medicines to treat various disorders such as bone fractures, rheumatism, diabetes, respiratory and pulmonary disorders, skin diseases, inflammatory ailments, diarrhea, and others. However, the currently available data on traditional and pharmacological uses have not been comprehensively reviewed., Study Aim: The present review is designed to provide information on the ethnobotanical uses, phytochemistry, toxicity, and the known biological properties of Sambucus, to understand their connotations and provide a scientific basis and gaps for further research., Materials and Methods: The information was obtained from different bibliographic databases, Google Scholar, Springer Link, Web of Science, PubMed, and Science Direct along with other literature sources such as dissertation before August 2021. The scientific names were validated using The Plant List and World Flora Online websites., Results: Twelve Sambucus species were found to be frequently mentioned in ethnomedical uses recorded in China, Korea, Turkey, Iran, and other countries. Traditionally, they have been used as remedies to numerous health complications among others, bone fractures and rheumatism, diabetes, wounds, inflammatory diseases, diarrhea, menstrual pains, respiratory and pulmonary complaints, skin disorders, headaches, snakebites, and urinary tract infections. To date, only eleven species have been studied for their chemical compounds and a total of 425 bioactive constituents, including phenolic compounds, terpenoids, fatty acids, cyanogenic glycosides, phytosterols, lectins, organic acids, alkaloid, coumarin, anthraquinone, and others have been reported. The crude extracts and the isolated chemical constituents exhibited diverse outstanding pharmacological activities including antioxidant, antimicrobial, antidiabetic, anti-inflammatory, antidepressant, analgesic, anti-giardial, immunomodulatory, scolicidal, anti-ulcerogenic, antiradical, bone-protective, anti-glycemic, antiosteoporotic, hypolipidemic, anti-glycation, and wound-healing properties., Conclusion: This study summarized and scrutinized the data on traditional uses, pharmacological activities, phytochemicals, and toxicity of Sambucus species, which indicate they have interesting chemical compounds with diverse biological activities. Many traditional uses of some species from this genus have now been confirmed by pharmacological activities, such as antioxidant, antimicrobial, bone-protective, wound healing, anti-inflammatory, and analgesic properties. However, the currently available data has several gaps in understanding the traditional uses of all Sambucus species. Thus, we strongly recommend further investigations into the scientific connotations between traditional medicinal uses and pharmacological activities, mode of action of the isolated bioactive constituents, and toxicity of other Sambucus species to unravel their efficacy and therapeutic potential for safe clinical application. The current extensive study avails valuable information on therapeutic use of Sambucus species and paves way for further investigations of other useful species, as well as drug discovery., (Copyright © 2022 Elsevier B.V. All rights reserved.)