Development of predictive, diagnostic, and prognostic biomarkers of allograft status and outcome is important and challenging, and may be rewarded with individualized therapy for the organ graft recipient. Herein, we summarize noninvasive messenger RNA profiling studies for ascertaining allograft status and outcome. Nucleic acid-based biomarkers of allograft status have been developed by several laboratories, but the studies have primarily been single center investigations. Ongoing multicenter trials including the Clinical Trials in Organ Transplantation (https://www.ctotstudies.org) should help further to define the clinical utility of noninvasively developed messenger RNA profiles as biomarkers of allograft status and outcome.