Three classes of organometallic complexes, metallocene diacidos Cp 2MX 2(M=Ti, V, Nb, Mo, Re), ferricenium salts and organotin compounds have been reported to exhibit impressive in vivo or in vitro antitumour activities against a range of tumour cell lines. Titanocene dichloride is currently on the phase II clinical trials. Biological studies suggest that DNA is one of the primary intracellular targets of the metallocene dihalides but their mechanism of action is poorly understood. By using various modern techniques, the binding modes of Cp 2TiCl 2, Cp 2VCl 2, Cp 2NbCl 2, Cp 2MoCl 2, Cp 2ZrCl 2, Cp 2Fe +X −, (CH 3) 2SnCl 2, (C 2H 5) 2SnCl 2, (C 2H 5) 2SnCl 2(phen) with DNA and nucleotides in aqueous solution have been investigated. The results show that all the above organometallic agents exhibit high affinity to phosphate group of nucleotides. In aqueous solution, 5′GMP(or 5′dGMP), 5′AMP, 5′CMP, 5′TMP with Cp 2TiCl 2 or Cp 2MoCl 2 form chelate complexes in which both base nitrogen atom and phosphate oxygen atom of nucleotides bind to the metal center; whereas the other organometallics may bind to dGMP via only the phosphate group. The interactions between Cp 2TiCl 2, Cp 2ZrCl 2, (CH 3) 2SnCl 2 or (C 2H 5) 2SnCl 2 with calf thymus DNA suggest that Cp 2TiCl 2(aq) may bind to both the base ring sites and the phosphate backbone of DNA; while other organometallics(aq) bind to DNA via only the phosphate group. In addition, the relationship between DNA binding property of metal anticancer complex and their anticancer activity is discussed and a hypothesis named ‘Two-Pole Complementary Principle’ is also put forward and some criteria are suggested as well.