Tumor targeting--per definition--includes any strategy to improve the specificity of the therapeutic nucleic acid towards the tumor site, while highest biological activity should be maintained. Targeting has been successfully achieved at the transcriptional, transductional or delivery level. For tumor-specific delivery, physical targeting methods like electroporation, hyperthermia, magnetofection, photochemical internalization or ultrasound, and biological targeting systems, including active and passive tumor targeting, have been developed. Therapeutic effects could be demonstrated with various targeted nucleic acid formulations, such as tumor-targeted DNA plasmids expressing p53 or tumor necrosis factor alpha, small interfering RNAs knocking down gene expression from tumor specific chromosomal translocations or gene expression of tumor neoangiogenic processes, as well as double stranded RNA poly inosine-cytosine which triggers apoptosis in targeted tumor cells.