Cancer continues to be a disease that is difficult to cure and the current therapeutic regimen is associated with severe side effects and the issue of emerging drug resistance. According to the World Health Organization fact sheet 2017, cancer is the second major cause of morbidity and death and a 70% rise in new cases is expected over the next 20 years. The quest for new anticancer chemical entities is a thrust area identified by many government agencies and industry research and development groups. Nature-derived entities have played a very important role in therapeutics especially cancer Asteraceae is a large family consisting of around 1700 genera and more than 24,000 species. Several genera belonging to this family have ethnopharmacological uses such as cytotoxicity, antidiabetic, hepatoprotective and antioxidant. This review highlights the cytotoxic potential of structurally novel flavonoids and sesquiterpenes isolated from some selected species of Asteraceae plants native to Asia, Europe, parts of Africa and America. The existing literature suggests that sesquiterpenes and flavonoids from various species of Asteraceae represent a viable class of secondary metabolites with strong cytotoxic potential. These have demonstrated potent activity in cell cycle arrest, inhibition of neoangiogenesis and induction of apoptosis. The sesquiterpenoids exhibiting potent cytotoxic activity were found to contain an α- methylene-butyrolactone conjugated with an exomethylene group and the flavonoids obtained from various plant species of Blumea suggest that a dihydroxy ring system present in structure is essential for activity. Most of the published literature contains in vitro data of extracts/secondary metabolites with very few in vivo studies. Additionally, there is dearth of knowledge on mechanisms of cytotoxic activity and molecular targets impacted by the active secondary metabolites. This review hopes to fuel interest in researchers to take up detailed investigations on these scaffolds that could contribute significantly as potential leads in anticancer drug development.