<p>Although transplantation remains a life-saving treatment for organ failure, long-term patient survival continues to be severely limited by the risk of allograft rejection. Preventing rejection remains a critical challenge despite significant advancements in surgical techniques, organ availability, and immunosuppressive therapies. The primary goal of transplantation research is to achieve immune tolerance to transplanted allografts. Although tissue biopsy remains the most reliable method for diagnosing acute rejection (AR), recent advances in molecular diagnostics have revealed novel genomic, transcriptomic, and proteomic biomarkers. These biomarkers hold significant potential for extending organ longevity by enabling early rejection detection and guiding personalized treatment strategies. Current surveillance transplanted patients relies heavily on serum biochemical tests, which help identify and treat asymptomatic rejection, a condition with excellent prognosis when addressed early. However, there is a critical need for non- or minimally invasive biomarkers that are both sensitive and reliable, capable of supplementing or replacing invasive biopsies, and reducing dependence on conventional biochemical markers. This study aimed to provide an overview of the available data on the importance of ncRNA expression patterns in predicting and monitoring transplant rejection, which offers a promising avenue for improving post-transplant outcomes.</p>