Predicting and diagnosing acute kidney allograft rejection by non-invasive biomarkers is a major goal in clinical transplantation research. Such biomarkers can be reduced to the various stages of the alloimmune response, from transcriptional regulation to immunological effector mechanisms. Here, we describe novel insights into exciting areas of transplantation-related biomarker research that may be translated to non-invasive monitoring strategies. First, we will elaborate on microRNAs, which represent stable, small non-coding ribonucleic acid molecules that can specifically regulate gene expression. Secondly, we will discuss novel methods to monitor human leukocyte antigen (HLA)-specific B cells, as well as the anti-HLA antibodies they produce. Incorporation of these new biomarkers and methodologies into cross-platform biomarker panels may help to improve non-invasive prediction and detection of allograft rejection.