Limited availability of data has hindered the development of algorithms that can identify functionally meaningful regulatory single nucleotide polymorphisms (rSNPs). Given the large number of common polymorphisms known to reside in the human genome, the identification of functional rSNPs via laboratory assays will be costly and time-consuming. Therefore appropriate bioinformatics strategies for predicting functional rSNPs are necessary. Recent data from the Encyclopedia of DNA Elements (ENCODE) Project has significantly expanded the amount of available functional information relevant to non-coding regions of the genome, and, importantly, led to the conclusion that many functional elements in the human genome are not conserved.