Nanotechnology is a rapidly evolving field that encompasses the fabrication and application of materials at the nanometer scale using either top-down approaches or bottom-up assembly. In the biological world, a large number of highly ordered structures and nanomachines made up of macromolecules have evolved to perform many diverse biological functions. Their intriguing configurations have inspired many biomimetic designs. DNA, RNA, and proteins have unique intrinsic characteristics at the nanometer scale and therefore can serve as the building blocks for the bottom-up design and construction of nano scale structures and devices. Seeman pioneered the concept 30 years ago of using DNA as a material for creating nanostructures; this has led to an explosion of knowledge in the now well-established field of DNA nanotechnology. The potential of using peptides and proteins for nanotechnological applications has also been extensively explored. Recently, RNA molecules have become increasingly attractive. The field of RNA nanotechnology is rapidly emerging. RNA can be manipulated with the simplicity characteristic of DNA to produce nanoparticles with a diversity of quaternary structures by self-assembly. Additionally RNA is tremendously versatile in its function and some RNA molecules display catalytic activities much like proteins. Thus, RNA has the advantage of both worlds. However, the instability of RNA has made many scientists flinch away from RNA nanotechnology. Other concerns that have deterred the progress of RNA therapeutics include the induction of interferons, stimulation of cytokines, and activation of other immune systems, as well as short pharmacokinetic profiles in vivo. This review will provide some solutions and perspectives on the chemical and thermodynamic stability, in vivo half-life and biodistribution, yield and production cost, in vivo toxicity and side effect, specific delivery and targeting, as well as endosomal trapping and escape.