Polymerase chain reaction (PCR) has become a standard and important molecular biological technique with numerous applications in genetic analysis, forensics and in vitro diagnostics. Since its invention in the 1980s, there has been dramatic performance improvement arising from long-lasting efforts to optimize amplification conditions in both academic studies and commercial applications. More recently, a range of nanometer-sized materials including metal nanoparticles, semiconductor quantum dots, carbon nanomaterials and polymer nanoparticles, have shown unique effects in tuning amplification processes of PCR. It is proposed that these artificial nanomaterials mimic protein components in the natural DNA replication machinery in vivo. These so-called nanomaterials-assisted PCR (nanoPCR) strategies shed new light on powerful PCR with unprecedented sensitivity, selectivity and extension rate. In this review, we aim to summarize recent progress in this direction and discuss possible mechanisms for such performance improvement and potential applications in genetic analysis (particularly gene typing and haplotyping) and diagnostics.