Agents that interfere with tubulin function have a broad anti-tumour spectrum and they represent one of the most significant classes of anti-cancer agents. In the past few years, several small synthetic molecules that have an azaflavone nucleus as a core structure have been identified as tubulin inhibitors. Among these, several arylquinolinones, arylnaphthyridinones, arylquinazolinones and arylpyrroloquinolinones have shown to exert their anticancer activity through inhibition of tubulin polymerisation via the colchicine binding site. They arrest the cell growth at G2/M phase providing cell death via both mitotic and apoptotic pathway. Recently, some of them proved to be multi-inhibitor simultaneously targeting both PI3K-Akt-mTOR pathway and the microtubule cytoskeleton. Furthermore, some were demonstrated to possess effective anti-angiogenic properties similar to that of natural compounds combretastatine-A4 and vincristine. This article reviews the synthesis, biological activities and SARs of the main classes of azaflavones. Brief mention of the subtype 2- styrylquinazolinones has also been made.