In the field of nonviral gene therapy, mRNA-based gene transfer has generated much interest over the last decade. The combination of RNA as a versatile protein delivery molecule and the dendritic cell as the most potent antigen-presenting cell is an attractive approach to induce cellular and potentially therapeutic immune responses in patients with cancer. The success of mRNA transfection stems from its superior cytoplasmic expression efficiency, simplicity over viral transduction protocols, and clinical safety profile (due to a strictly transient expression and inability to integrate into the host genome). Most researchers have exploited low-voltage electrical pulses (electroporation) as a means to introduce RNA into cells, but other methods with an even higher degree of in vivo applicability are under development. Recently, more insights into the immunological properties of RNA and optimized strategies to produce highly translatable mRNA have increased its efficacy in cellular vaccination. In addition, application of RNA gene transfer into areas other than immunotherapy are slowly emerging and underscore the potential of RNA transfection as a versatile gene therapy tool.