Since the first edition of this book in 1999 the field of gene therapy has been the arena both for major advances that justified the early hopes placed in the concept, and for ever-present impatience with the slowness of overall progress. On the positive side, gene therapy obtained its first brilliant success, though not where most efforts were invested and not with a synthetic vector (Cavazzana-Calvo et al., 2000). Yet the search for efficient molecules is still very active, in part because the negative consequences of using viral vectors somewhat shadow the brilliant picture (Hacein-Bey-Abina et al., 2003). Clinical trial reports using the first generation of non-viral vectors, that is, cationic lipids, emphasize safety more than efficacy. The next generation, namely cationic polymers, is coming to maturity. This is illustrated in Fig. 8.1 by a literature survey that compares the most used "open source" vector in each category, the lipid DOTAP and polymer PEI. This "coming of age" is also highlighted by the number of planned clinical trials using PEI, trials we shall discuss in the last paragraph of this chapter. Advances have not only been made toward therapy, but also toward a better understanding of the mechanisms underlying gene delivery. Finally, PEI has become one of the most popular reagents for transfection of cells in culture, on a fast-growing market that is boosted by human and animal genome sequencing.