Gene therapy research is still in trouble owing to a paucity of acceptable vector systems to deliver nucleic acids to patients for therapy. Viral vectors are efficient but may be too dangerous. Synthetic non-viral vectors are inherently safer but are currently not efficient enough to be clinically viable. The solution for gene therapy lies with improved synthetic non-viral vectors systems. This review is focused on synthetic cationic liposome/micelle-based non-viral vector systems and is a critical review written to illustrate the increasing importance of chemistry in gene therapy research. This review should be of primary interest to synthetic chemists and biomedical researchers keen to appreciate emerging technologies, but also to biological scientists who remain to be convinced about the relevance of chemistry to biology.