Rice (Oryza sativa L.) is continuously challenged by various biotic stresses including fungal, bacterial, viral, parasites, and insect pests. These stresses threaten global rice productivity each year. Numerous resistance (R) genes have been identified, but only a few of them have been deployed in rice improvement programs due to the rapid breakdown of resistance, pleiotropic effects, and negative associations with important agronomic traits. Modern varieties are being developed by pyramiding multiple R-genes from diverse germplasm. However, unregulated expression of R-genes often comes with unexpected yield trade-offs and poor plant fitness. MicroRNAs (miRNAs) are endogenous, short, single-stranded, non-coding RNA molecules that function as master regulators for balancing immunity and yield. Defense-related miRNAs such as Osa-miR156, Osa-miR162, Osa-miR396, and Osa-miR1873 have been identified in rice that fine-tunes immunity and yield under various biotic stresses. Recent advances showed that many immune-responsive miRNAs also regulate many complex traits of agronomic importance. This allows researchers to assemble the appropriate combinations of agriculturally important traits to be targeted using genetic engineering approaches that involved miRNAs.