In the post-genomic era, the goal of personalized medicine is to determine the correlation between genotype and phenotype. Developing high-throughput genotyping technologies such as genome-wide association studies (GWAS) and the 1000 Genomes Project (http://www.internationalgenome.org/about/#1000G-PROJECT) has dramatically enhanced our ability to map where changes in the genome occur on a population level by identifying millions of single nucleotide polymorphisms SNPs). Polymorphisms, particularly those within the coding regions of proteins and at splice junctions, have received the most attention, but it is also now clear that polymorphisms in the non-coding regions are important. In these non-coding regions, the enhancer and promoter regions have received the most attention, whereas the 30 -UTR regions have until recently been overlooked. In this review, we examine how SNPs affect microRNA-binding sites in these regions, and how mRNA stability changes can lead to disease pathogenesis.