MicroRNAs (miRNAs), approximately 19-25 nucleotides in length, are posttranscriptional regulators of protein expression that target and inhibit translation of messenger (m) RNAs. Recent research on miRNAs has produced a plethora of new material on the role of miRNAs in disease. Deregulation or ablation of miRNA expression has led to major pathologies including heart disease and cancer. Signatures of differential miRNA expression have been uncovered for nearly every disease. Recent research has focused on exploitation of the selectivity of these signatures as markers of disease and for therapeutic applications. The significance of additional mechanisms of abnormal posttranscriptional regulation, such as ultraconserved genes (UCGs), has recently been recognized. This review focuses on the identification of aberrant posttranscriptional regulators (miRNAs and UCGs) in cancer and cardiovascular disease and addresses the applications of this work towards diagnosis and therapy.