The unique ability to rapidly amplify low copy number DNA has made in vitro Polymerase Chain Reaction one of the most fundamental techniques in modern biology. In order to harness this technique to its full potential, certain obstacles such as nonspecific by-products, low yield and complexity of GC rich and long genomic DNA amplification need to be surmounted. As in vitro PCR does not have any regulatory mechanisms unlike its counterpart in vivo DNA replication machinery, scientists often use a number of additives like glycerol, betaine, dimethyl sulphoxide and formamide in order to achieve the perfection of in vivo systems. In the last two decades nanotechnology has provided excellent solutions to many classical problems in various scientific fields including biotechnology and recently the PCR technique has begun to benefit from this so called “Nano Era”. In this review, the impacts of several nanomaterials on PCR efficiency, specificity and fidelity are described in accordance with the recent literature. Putative interaction mechanisms between nanomaterials and primary PCR components are also addressed in a comprehensive manner.