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Objective: Rapid advances of high-throughput technologies and wide adoption of electronic health records (EHRs) have led to fast accumulation of –omic and EHR data. These voluminous complex data contain abundant information for precision medicine, and big data analytics can extract such knowledge to improve the quality of healthcare. Methods: In this paper, we present –omic and EHR data characteristics, associated challenges, and data analytics including data preprocessing, mining, and modeling. Results: To demonstrate how big data analytics enables precision medicine, we provide two case studies, including identifying disease biomarkers from multi-omic data and incorporating –omic information into EHR. Conclusion: Big data analytics is able to address –omic and EHR data challenges for paradigm shift toward precision medicine. Significance: Big data analytics makes sense of –omic and EHR data to improve healthcare outcome. It has long lasting societal impact. [ABSTRACT FROM AUTHOR]