Allele-specific polymerase chain reaction (PCR), a method that reports nucleotide variations through either the presence or the absence of a DNA product obtained through PCR amplification, holds the promise to combine target amplification and analysis in one single step. Recently, it has been reported that the selectivity of allele-specific PCR can be significantly increased through the employment of chemically modified primer probes. Here, we report on significant developments of primer probe design and synthesis along this line.