Striated muscle tissue is an attractive target for gene delivery as it can be easily reached and can express exogenous proteins. However, administration of naked DNA results in low transfection levels, and the design and development of safe and efficient gene delivery systems are thus required. This review is focusing on the characteristics of the striated muscle tissue with regards to features possibly affecting gene transfer, as well as the different soluble polymers that have been evaluated as gene carriers. The described formulations are ranging from polymers displaying a high density of positive charges to non-ionic molecules. Nevertheless, polymers exhibiting few or no positive charges appear to our opinion as the most promising approach to achieve both safe and efficient transfection of the striated muscles.