MicroRNAs (miRNAs) are evolutionarily conserved, small ( approximately 20-25 nucleotides), single-stranded molecules that suppress the expression of protein-coding genes by translational repression, messenger RNA degradation, or both. More than 700 miRNAs have been identified in the human genome. Amazingly, a single miRNA can regulate the expression of hundreds of mRNAs or proteins within a cell. The small RNAs are fast emerging as master regulators of innate and adaptive immunity and likely to play a pivotal role in transplantation. The clinical application of RNA sequencing ("next-generation sequencing") should facilitate transcriptome profiling at an unprecedented resolution. We provide an overview of miRNA biology and their hypothesized roles in transplantation.