A systems approach to blood diseases can help make essential contributions to our ability to diagnose, treat, and perhaps even prevent common diseases in humans. Using blood as a window, one can study health and disease through this unique tool box with reactive biological fluids that mirrors the prevailing hemodynamics of the vessel walls and the various blood cell types. Many blood diseases, rare and common, can and have been exploited using systems biology approaches with successful results and therefore ideal models for systems medicine. More importantly, hematopoiesis offers one of the best studied systems with insight into stem cell biology, cellular interaction, development; linage programming and reprogramming that are influenced every day by the most mature and understood regulatory networks.