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ETHNOPHARMACOLOGICAL RELEVANCE Chromolaena species, of the Asteraceae family, are distributed across the tropical and the temperate regions of Africa, the Americas, southern Asia, and Australia. Despite "falling out of favour" among the people because of their "weedy" nature, Chromolaena species have indisputable long medicinal history in the treatment of malaria, nasal congestion, inflammation, eye disorders, asthma, cough, flu, headache, and cold. AIM OF THE REVIEW The aim of this review is to systematically summarize the current knowledge on ethnopharmacology, phytochemistry, pharmacology, toxicology, and real-time scientific applications of the genus Chromolaena after re-classification from genus Eupatorium, as well as to proffer integrated approaches in maximizing their therapeutic values despite their "weedy" nature. MATERIALS AND METHODS First, the current species in the genus were verified by "The Plant List" (http://www.theplantlist.org) and "Royal Botanic Gardens/Kew/Missouri Botanical Garden" (http://mpns.kew.org/mpns-portal/). Second, the relevant information on each of the identified species was gathered from following databases: Google Scholar, Online Wiley library, ScienceDirect, SciFinder, Scopus, PubMed. Scientific literature was searched from inception till August 2021. RESULTS More than 190 phytochemicals have been isolated and identified from 27 species of the genus, including flavonoids, alkaloids, triterpenoids, diterpenoids, sesquiterpenoids, steroids, fatty acids, and coumarins among others. Pharmacological investigations, both in vitro and in vivo, have shown that the extracts and the compounds have antimicrobial, anticancer, antioxidant, insecticidal, anti-inflammatory, and anti-diabetic activities among others. CONCLUSIONS Many species of genus have potential therapeutic values, and hence they are more than "wandering" weeds. In addition, there is growing interest in the real-time scientific applications of the genus in the production of pharmacological polyherbal products, and this should serve as a stimulus to strategically develop integrated control approaches for preserving these species, with a view of maximizing their therapeutic values and reducing their cost of eradication.