Saponins are a group of naturally occurring plant glycosides, characterized by their strong foam-forming properties in aqueous solution. The presence of saponins has been reported in more than 100 families of plants out of which at least 150 kinds of natural saponins have been found to possess significant anti-cancer properties. There are more than 11 distinguished classes of saponins including dammaranes, tirucallanes, lupanes, hopanes, oleananes, taraxasteranes, ursanes, cycloartanes, lanostanes, cucurbitanes and steroids. Due to the great variability of their structures, saponins always display anti-tumorigenic effects through varieties of antitumor pathways. In addition, there are a large amount of saponins that still either remain to be trapped or studied in details by the medicinal chemists. This article reviews many such structures and their related chemistry along with the recent advances in understanding mechanism of action and structure-function relationships of saponins at the molecular and cellular levels. These aglycones have been described and their classification and distribution have been listed in the review. Some special saponins with strong antitumor effects have also been exhibited. Ginsenosides, belonging to dammaranes, have been found beneficial targeted on inhibition of tumor angiogenesis by suppressing its inducer in the endothelial cells of blood vessels, and then on prevention of adhering, invasion, and metastasis of tumor cells. Dioscin, one of the steroidal saponins, and its aglycone diosgenin also have been extensively studied on its antitumor effect by cell cycle arrest and apoptosis. Other important molecules discussed include oleanane saponins such as avicins, platycodons, saikosaponins, and soysaponins along with tubeimosides.