Throughout history, the development of medical imaging has evolved alongside clinical practice. Early innovations like X-rays open the era of non-invasive imaging of anatomical skeletons. Ultrasound, CT, and MR improve the resolution of tissue structures across different scales. With the emergence of PET and SPECT, molecular imaging employs tracers to map metabolic activities. Further progress in optical molecular imaging achieves high-resolution real-time visualization of biological processes at the molecular and cellular levels. This chapter outlines the historical progression from traditional medical imaging to molecular functional imaging and optical molecular imaging, emphasizing the potential of multimodal technology integration, biomarker exploration, and precision medicine. It briefly discusses current challenges faced by optical molecular imaging in technical optimization and clinical applications.