This chapter explores how medical imaging has evolved beyond simple visual observation to include advanced optical technologies for disease detection. Traditionally, clinicians relied heavily on human vision, either directly or through video systems, for identifying abnormalities during examinations, surgeries, and endoscopic procedures. While high-definition white-light and stereoscopic imaging enhance these capabilities, they still fundamentally depend on what the human eye can distinguish. Optical coherence tomography (OCT) marked a significant advance by providing high-resolution images below the tissue surface, particularly benefiting ophthalmology and, more recently, cardiology. However, OCT is limited to morphological contrast and cannot capture molecular information. Thus, this chapter introduces two innovative light-based modalities. The first modality, Fluorescence Molecular Imaging (FMI), leverages targeted fluorescent agents to highlight molecular features in living tissues. Recently, FMI has moved beyond older approaches that used non-specific dyes like Indocyanine Green (ICG) to targeted dyes that enable visualization of molecular details. The second modality, optoacoustic imaging, uses light to excite ultrasound waves within tissue to generate high-resolution images at greater depths than traditional optical techniques. This modality can resolve spectral signatures of molecules or agents, providing comprehensive views of tissue structure, function, and molecular composition. Together, these advances in FMI and optoacoustic imaging promise more sensitive, specific, and non-invasive disease detection and characterization, signaling a new era in clinical imaging.