The explosion of genetic information from recent advances in sequencing technologies, bioinformatics and genomics highlights the importance of understanding mechanisms involved in gene expression and regulation. Over the last decade, it has become clear that small ribonucleic acids (RNAs) are a central component of the cellular gene regulatory network. MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNA of approximately 22 nucleotides in length that act as posttranscriptional gene regulatory elements. MicroRNAs can inhibit de novo protein synthesis by blocking translation through base-pairing with complementary messenger RNA (mRNA) and also suppress translation by promoting degradation of target mRNA. MicroRNAs are intimately involved in a variety of biologic processes including development, hematopoietic cell differentiation, apoptosis and proliferation. To date, over 800 human miRNAs have been identified, though the biologic function of only a fraction of miRNAs has been elucidated. Here, we discuss how miRNAs are produced, identified and quantitated, and focus on several key miRNAs that govern expression of genes relevant to allograft rejection, tolerance induction and posttransplant infection. Finally, we discuss potential ways in which the miRNA network can be modulated that ultimately may offer new strategies to promote long-term graft survival.