Natural killer (NK) cells play an important role in the direct killing of cancerous and virus-infected cells. One of the important activating receptors which mediates this killing is NKG2D. This receptor recognizes various stress-induced ligands including the major histocompatibility complex class I-related chain A and B (MICA and MICB respectively). The mechanisms controlling the expression of the NKG2D ligands are not completely understood, yet various studies have demonstrated that the expression of the NKG2D ligands is manipulated by viruses and by tumor cells in order to escape the NKG2D detection. Cumulative data have emphasized that various microRNAs (miRNAs) of both human and viral origin control the expression of NKG2D ligands, particularly MICB. Herein we review recent findings regarding the miRNA regulation of the NKG2D ligands. We propose that these miRNAs generate a complex network of interactions that control the expression of the NKG2D ligands under normal conditions and during disease development.