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Isoxazolines are an important class of nitrogen and oxygen containing heterocycles that belong to the azoles family which have gained much importance in the field of medicinal chemistry as the anticancer agents. Moreover, natural products are always expectedly regarded as an important hoard of a large number of potential chemotherapeutic candidates. Therefore, this review mainly focuses on the existence of isoxazoline derivatives in natural sources, their isolation and uses there of as anticancer agents besides highlighting the synthetic pathways to achieve these compounds. Structural–activity relationship and the influence of stereochemical aspects on anticancer activity of such compounds have also been discussed. It covers the literature upto 2014 and would certainly provide a great insight to scientific community to accelerate further research for the development of some novel anticancer drugs.