Gene therapy holds great promise for treating a variety of human diseases and conditions. The field of gene therapy has advanced rapidly in the last decade. However, a major limiting factor remains the lack of a suitable vector for gene delivery. Although viruses are currently the most commonly researched vector, because of continuing safety concerns research has broadened to developing nonviral alternatives. Nonviral vectors fall into several categories. They can be physical methods, which provide relatively crude delivery approaches, such as direct cell injection, or chemical delivery vehicles. Chemical vectors almost always include a polycation component to assist the passage of DNA to the cell's nucleus. The passage of the transgene through the cell to the nucleus is hampered by many obstacles. Approaches to overcome these, both intracellularly and extracellularly, in order to maximize gene expression are currently under investigation. Nonviral vectors offer a safe and versatile alternative to their viral counterparts. Although still in their infancy, the different nonviral approaches under development hold great potential for many clinical applications.