Congestive heart failure affects about 23 million people worldwide, and cardiac allograft transplantation remains one of the last options for patients with terminal refractory heart failure. Besides the infectious or oncological complications, the prognosis of patients after heart transplantation is affected by acute cellular or antibody-mediated rejection and allograft vasculopathy development. Current monitoring of both conditions requires the performance of invasive procedures (endomyocardial biopsy sampling and coronary angiography or optical coherence tomography, respectively) that are costly, time-demanding, and non-comfortable for the patient. Within this narrative review, we focus on the potential pathophysiological and clinical roles of microRNAs (miRNAs, miRs) in the field of cardiac allograft transplantation. Firstly, we provide a general introduction about the status of cardiac allograft function monitoring and the discovery of miRNAs as post-transcriptional regulators of gene expression and clinically relevant biomarkers found in the extracellular fluid. After this general introduction, information from animal and human studies are summarized to underline the importance of miRNAs both in the pathophysiology of the rejection process, the possibility of its modulation by altering miRNAs levels, and last but not least, about the use of miRNAs in the clinical practice to diagnose or predict the rejection occurrence.