Personalized medicine is expected to benefit from the combination of genomic information with the global monitoring of molecular components and physiological states. To ascertain whether this can be achieved, we determined the whole genome sequence of an individual at high accuracy and performed an integrated Personal Omics Profiling (iPOP) analysis, combining genomic, transcriptomic, proteomic, metabolomic, and autoantibodyomic information, over a 38-month period that included healthy and two virally infected states. Our iPOP analysis of blood components revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways across healthy and disease conditions. Importantly, genomic information was also used to estimate medical risks, including Type 2 Diabetes, whose onset was observed during the course of our study. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states.