Publication of the human proteome has prompted efforts to develop high-throughput techniques that can catalogue and quantify proteins and peptides present in different tissue types. The field of proteomics aims to identify, quantify, analyze, and functionally define a large number of proteins in cellular processes in different disease states on a global scale. Peptidomics, a newer name in the -omics world, measures and identifies naturally occurring low molecular weight peptides, also providing an insight into enzymatic processes and molecular events occurring in the system of interest. One area of major interest is the use of proteomics to identify diagnostic and prognostic biomarkers for different diseases as well as for various clinical phenotypes in organ transplantation that can advance targeted therapy for various forms of graft injury. Outcomes in organ transplantation can be potentially improved by identifying noninvasive biomarkers that will serve as triggers that predate graft injury, and can offer a means to customize patient treatment by differentiating among causes of acute and chronic graft injury. Proteomic and peptidomic strategies can be harnessed for frequent noninvasive measurements in tissue fluids, allowing for serial monitoring of organ disease. In this review, we describe the basic techniques used in proteomic and peptidomic approaches, point out special considerations in using these methods, and discuss their applications in recently published studies in organ transplantation.