While the completion of the Human Genome Project has amplified the opportunities of personalized medicine, personalized medicine is not limited to the use of genetic information. This thesis synthetizes the work we have done on different genetic and/or non‐genetic aproaches to personalize general internal medicine. To illustrate the concept of personalized general internal medicine, we use three specific domains commonly encountered in general internal medicine (osteoporosis, cardiovascular disease, and cancer), and present three different approaches to potentially personalized care (biological markers, genetic markers,and shared‐decision making). We discuss the perspectives of using geographic information system and network analysis to personalize general internal medicine. The limitations, challenges, and need to demonstrate the clinical utility of personalized general internal medicine are acknowledged. This thesis is based on work done across a wide spectrum of disease and traits, but with the core motivation of demonstrating that internal medicine is general, yet personalized!