Precision medicine is an emerging integrative approach for disease prevention, early detection, and treatment which takes into account individual variability in genetic and other molecular measurements, medical history, environmental exposures, and lifestyle. The development and availability of genomic and other molecular profiling technologies provide an unprecedented opportunity to apply precision medicine strategies in transplantation research. Developing integrative computational methods to analyze these diverse types of data provides new opportunities to impact diagnostics and therapeutics. In this article, we discuss ways we can leverage molecular data sets to develop new hypotheses for disease mechanisms, identify new disease biomarkers, and reposition drugs for diseases with unmet needs. We specifically discuss computational methods that can be applied to achieve these goals in the context of organ transplant.