Gene delivery using nonviral approaches has been extensively studied as a basic tool for intracellular gene transfer and gene therapy. In the past, the primary focus has been on application of physical, chemical, and biological principles to development of a safe and efficient method that delivers a transgene into target cells for appropriate expression. This review summarizes the current status of the most commonly used nonviral methods, with an emphasis on their mechanism of action for gene delivery, and their advantages and limitations for gene therapy applications. The technical aspects of each delivery system are also reviewed, with a focus on how to achieve optimal delivery efficiency. A brief discussion of future development and further improvement of the current systems is intended to stimulate new ideas and encourage rapid advancement in this new and promising field.