The untranslated regions of mRNAs can determine gene expression by influencing mRNA stability and translational efficiency. Recent reports show that gene expression can be regulated by the differential use of alternative untranslated regions. Tissue-specific expression of transcripts that have different untranslated regions (UTRs) can control protein expression enabling developmental, physiological and pathological regulation. Several examples of alternative UTRs have been characterized, including those found in AXIN2, FGF1 and BRCA1. Results from bioinformatics studies indicate that this mechanism is more common than previously appreciated.