Polymerases with a proofreading function in their internal 3′ to 5′ exonucleasepossess high fidelity for DNA replication both in vivo and in vitro.The obstaclefacing Exo+ polymerases for single nucleotide polymorphism (SNP) detection couldbe bypassed by using primer-3′-termini modification.This hypothesis has beenwell tested using three types of modified allele specific primers with:3′ labeling,3′to 5′exonuclease resistance,and 3′dehydroxylation.Accordingly,three new SNPassaying methods have been developed to carry out genome-wide genotyping,taking advantage of the enzymatic properties of Exo~+ polymerases.These newmutation detection assays are widely adaptable to a variety of platforms,includ-ing multi-well plate and microarray technologies.Application ofExo~+ polymerasesto genetic analysis,including genotyping that is mostly relevant to pharma-cogenetics,high-fidelity gene expression profiling,rare mutation detection andmutation load assay,will help to accelerate the pace of personalized medicine.Inthis review paper,we will first introduce three new assays that we have recentlydeveloped,and then describe a number of their applications in pharmacogeneticsand in other biomedical studies. Polymerases with a proofreading function in their internal 3 ’to 5’ exonucleasepossess high fidelity for DNA replication both in vivo and in vitro. Obstinate Exo + polymerases for single nucleotide polymorphism (SNP) detection could be bypassed by using primer-3’-termini modification. This hypothesis has been tested using three types of modified allele specific primers with: 3 ’labeling, 3’to 5’exonuclease resistance, and 3’dehydroxylation. Accredited, three new SNP Assaying methods have been developed to carry out genome-wide genotyping, taking advantage of the enzymatic properties of Exo ~ + polymerases. the new assay detection assays are widely adaptable to a variety of platforms, includ-ing multi-well plates and microarray technologies. Application of Exo ~ + polymerasesto genetic analysis, including genotyping that is mostly relevant to pharma-cogenetics, high-fidelity gene expression profiling, rare mutation detection and mobility assay, will help to accelerate the pa ce of personalized medicine.Inthis review paper, we will first introduce three new assays that we have recently found, and then describe a number of their applications in pharmacogeneticsand in other biomedical studies.