Plants have provided the basis of traditional medicine systems throughout the world for thousands of years and continue to yield molecules for new remedies. We analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae), including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa, A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here, we report and discuss the mechanisms of action and structure-activity relationships of the most active Annona constituents. Annonaceous acetogenins are one of the most promising classes of natural products, owing to their potential antitumor activity. However, their neurotoxicity should not be underestimated.