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Optical imaging is a powerful modality in biological discovery. The mainstream of optical interrogations, however, largely relies on microscopy, which imposes depth limitations on resolving novel classes of optical reporter agents developed for in vivo use, such as fluorescent proteins and probes, other chromophoric molecules, and nanoparticles with specificity to cellular and subcellular activity. We review herein emerging optoacoustic (also termed photoacoustic) technologies that allow the visualization of optical reporter agents with never-seen-before visualization performance, enabling volumetric quantitative molecular imaging in entire organs, small animals, or human tissues. Multiwavelength/multispectral optoacoustic (photoacoustic) methods, in particular, allow for highly specific molecular imaging through several millimeters to centimeters of tissue with resolutions in the 20-200 μm range, combining high …