Prion diseases are associated with the accumulation in the brain of an abnormal, protease resistant isoform of a host encoded glycoprotein known as prion protein (PrP). Nanotechnology in combination with biotechniques promises a broad spectrum of highly innovative approaches for overcoming the challenges posed by the prions. Recent advances in molecular nanobiotechnology have brought in the potential of molecular targeting in diagnosis and therapies of various diseases. Their high binding sensitivity and specificity added by their small size have favored the identification by in vitro protocols. Molecular targeting has initiated exciting technologies based on conjugation of biomolecules to nanoparticles. This review article is an extensive study of various research oriented nanobiotechnological protocols for rapid identification and cure for prion diseases both at in vivo and in vitro options. © 2012 Praseetha PK, et al.