Single nucleotide polymorphisms (SNPs) are widely distributed in the human genome and although most SNPs are the result of independent point-mutations, there are exceptions. When studying distances between SNPs, a periodic pattern in the distance between pairs of identical SNPs has been found to be heavily correlated with periodicity in short tandem repeats (STRs). STRs are short DNA segments, widely distributed in the human genome and mainly found outside known tandem repeats. Because of the biased occurrence of SNPs, special care has to be taken when analyzing SNP-variation in STRs. We present a review of STRs in the human genome and discuss molecular mechanisms related to the biased occurrence of SNPs in STRs, and its implications for genome comparisons and genetic association studies.