MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level by degrading or blocking translation of messenger RNA (mRNA) targets. MiRNAs play important regulatory roles in a variety of cellular functions as well as in several diseases, including cancer. MiRNA-specific expression profiles have been reported for several pathological conditions. Recently, the discovery of miRNAs in serum opens up the possibility of using miRNAs as biomarkers of disease. In this review, we discuss the potential use of miRNAs as clinically diagnostic biomarkers of various cancers and other diseases as well as the approaches used to detect these molecules in serum and plasma.