Macroscopic optical imaging has rather humble technical origins; it has been mostly implemented by photographic means using appropriate filters, a light source and a camera yielding images of tissues. This approach relates to human vision and perception, and is simple to implement and use. Therefore, it has found wide acceptance, especially in recording fluorescence and bioluminescence signals. Yet, the difficulty in resolving depth and the dependence of the light intensity recorded on tissue optical properties may compromise the accuracy of the approach. Recently, optical technology has seen significant advances that bring a new performance level in optical investigations. Quantitative real-time multi-spectral optical and optoacoustic (photoacoustic) methods enable high-resolution quantitative imaging of tissue and disease biomarkers and can significantly enhance medical vision in diagnostic or interventional procedures such as dermatology, endoscopy, surgery, and various vascular and intravascular imaging applications. This performance is showcased herein and examples are given to illustrate how it is possible to shift the paradigm of optical clinical translation.