Cancer is still considered a “hopeless case”, besides all of the advancements in oncology research. On the other hand, the natural products, as effective lead molecules, have gained significant interest for research due to the absence of toxic and harmful side effects usually associated with conventional treatment methods. Medicinal properties of herbal plants are strongly evidenced in traditionalmedicine fromancient times. In the context above, withaferin A (WA) was identified as the active principle of the plant Withania somnifera, its molecule being reported to have excellent anticancer and tumour inhibition activities in various cell lines. Furthermore, the in silico approaches in the medicinal chemistry ofWA revealed the biological targets and gave momentum for the research that leads to many amazing pharmacological activities of WA which are not yet explored. This includes a broad spectrum of anticancer actionsmanifested in different organs (breast, pancreas, colon), melanoma and B cell lymphoma, etc. This review is an extensive survey of the most recent anticancer studies reported for WA, along with its mechanism of action and details about its in vitro and/or in vivo behaviour.