This chapter discusses the engineering concept of systems integration and its potential applications in medicine. With its goal of improving efficiency and cost saving, systems integration could potentially provide the needed improvement for the healthcare delivery in the US. After a brief introduction to the engineering concept of systems integration, this chapter deals with systems integration in medicine in two areas: integration of healthcare delivery and integration of science and clinical practice. Medical examples were utilized to illustrate this point. Many challenges are envisioned in the pursuit of systems integration in medicine, including individual physician preference, medical-legal issues, billing and reimbursement issues, and capital funding requirement for infrastructures. While challenges will be encountered, the medical community, along with a supporting society, would be able to overcome the difficulties to achieve the objectives.