We will focus on the therapeutic applications of ultrasound (US) for gene transfection or 'sonoporation'. Sonoporation therapy or 'sonotherapy' is an emerging physical method for delivering drugs and/or nucleic acids for treating cancer. Because of its non-invasive nature, sonotherapy has the potential to be competitive with other treatment delivery methods such as viruses or lipofection. For nucleic acid delivery, sonoporation in the presence of microbubbles (MB) significantly enhances transfection efficiency. Sonoporation is an ideal means of delivering pDNA, and it has a similar efficiency as electroporation or other physical gene therapy techniques, with potentially fewer side effects. Typically, nonphysical means of gene delivery have suffered from lower efficiencies compared to viral vectors, however, several studies suggest that sonoporation pDNA delivery could be a simple and inexpensive method that only requires a plasmid, MB, and a sonoporation device. Sonoporation could also be used to target MB to certain cells/tissues, delivering localized therapies. Using high-performance probes, more precise and safer sonoporation treatments will be developed, and newer therapeutic prospects will be realized.