Acute kidney injury (AKI) is a devastating clinical condition, both in terms of mortality and costs, and is occurring with increasing incidence. Despite better clinical care, the outcomes of AKI have changed little in the last 50 years. This lack of progress is due in part to a lack of early diagnostic biomarkers and a poor understanding of the disease mechanisms. This review will focus on the rapid progress being made in both the understanding of AKI and the promising panel of early biomarkers for AKI that have come out of both direct proteomic analysis of body fluids of AKI patients and more targeted proteomic approaches using clues from other methods such as transcriptomics. This review concludes with a discussion of the future of proteomics and personalized medicine in AKI and the challenges presented in translating these exciting proteomic results to the clinic.