Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. Many cationic lipids and cationic polymers naturally occurred or synthesized have been used for gene transfer. They have the advantages over viral gene transfer as non-immunogenic, easy to produce and not oncogenic. These cationic compounds, however, have the major limitations of inefficient transfection and toxicity to cells. For overcoming these problems, many new cationic compounds were developed since the first cationic lipid, DOTMA, was found usage in gene therapy. This article reviews cationic lipids for gene therapy from chemistry viewpoint and we classify these compounds as monovalent cationic lipids, polyvalent cationic lipids, cationic polymers, guanidine containing compounds, cationic peptides and cholesterol containing compounds, and hope to provide suggestions on the development of this variety of cationic compounds through the discussion. (C) 2004 Elsevier B.V. All rights reserved.