Targeting therapeutic genes to tumors is an attractive concept in curing malignant diseases. Systemic gene delivery systems are needed for therapeutic applications in which the target cells are not directly accessible, and which can only be reached via the systemic route. Recent developments in the field of non-viral gene delivery have shown that, based on (poly)cationic carrier molecules, DNA can be efficiently targeted to tumors via the bloodstream. Tailor-made synthetic vectors can be used to achieve predominant gene expression in tumor tissue. Therapeutic concepts based, for example, on suicide genes or cytokines, showed encouraging results in preclinical and also in first clinical evaluations.