Citrus essential oil (CEO) is obtained from the fruit of Genus Citrus, a flowering plant shrub in the family of the Rutaceae (Eremocitrus or Microcitrus) and extensively used in food, chemical industry, and traditional medicinal treatment owing to its pleasant aroma, antioxidant, and antiseptic properties. This review presents a botanical description, distribution, traditional uses, chemical composition, bioactive components, and the therapeutic uses as well as toxicological effects of the CEO. The objective was achieved via a comprehensive literature search of electronic databases such as Science Direct, PubMed, Web of Science, Wiley, ACS, Springer, Taylor and Francis, Google Scholar, SCOPUS, conference proceedings, thesis, and books until 2022 for publications. Citrus essential oils and their constituents are extracted and isolated either from the fruit peels, seeds, leaves, or flowers of the citrus plants. A comparative study of the sources of CEO confirmed its origin, ethnopharmacological and therapeutic uses. Over 2000 secondary metabolites have been isolated, with the main active constituents: being terpenes, monoterpenes, sesquiterpenes, and diterpenes. A comprehensive literature review revealed vast therapeutic benefits of CEO. Incomplete data report on in vitro and in vivo trials especially, on dosage, positive and negative control groups, intervention time, toxicity studies, phytochemical profiling, and clinical trials seem to be a knowledge gap.