DNA topoisomerases are enzymes involved in various aspects of genetic processes by catalyzing a topological change of DNA. Topoisomerase is now viewed as an important cellular target of antitumor drugs. These drugs targeting topoisomerase have been used to establish a relationship between drug-induced cleavable complex formation and cytotoxicity. Topoisomerase I is shown to be the cellular target of camptothecin and its derivatives. And topoisomerase II targeting drugs are both intercalative drugs (acridines, ellipticines, anthracyclines) and non-intercalative drugs (epipodophyllotoxin derivatives). And then Irinotecan, topotecan, sobuzoxane and IST-622 are unique topoisomerase inhibitors and are under investigation in Japan, the new antitumor drugs targeting topoisomerases are reviewed.