Background: Eucalyptus genus members have received a great interest worldwide for their antibacterial, antiviral, antifungal, anti-inflammatory and insect-repellent properties for cosmetic, pharmaceutical, nutraceutical and furniture purposes. Indeed, the application of Eucalyptus essential oil in cosmetic and personal hygiene products is gradually increasing. Also, it has been widely used in the traditional medicine for centuries, in the treatment of respiratory diseases, common cold, influenza, and sinus congestion. Scope and approach: This review addressed botanical and ethnopharmacological aspects of Eucalyptus plants, as also its in vitro and in vivo pharmacological activities, and current insights with regards to clinical efficacy and safety. Key findings and conclusions: Eucalyptol (1,8-cineole) is the main component present in Eucalyptus oils. According to the previously reported uses of Eucalyptus oils and extracts, there is urgently required further in vivo studies with the distinct Eucalyptus constituents to reveal the secrets beyond the traditional uses for treatment of a wide spectrum of ailments. A great attention has also been given for its nanotechnological applications by food and pharmaceutical industries. Nanoemulsions containing Eucalyptus globulus oil have been recognized for its antimicrobial and antibiofilm effects against gram-negative bacteria and the major microorganism responsible for causing fungal infections worldwide (Candida albicans). Moreover, eucalyptol does not present genotoxicity or carcinogenicity. Subacute hepatotoxic and nephrotoxic effects in animal models have been stated after application of high doses, higher than the estimated LD50 (2400 mg/kg b.w. In rats). However, an in-deep risk assessment on further exposure and toxicity data is highly needed.