AbstractOptoacoustic (OA, photoacoustic) imaging capitalizes on the synergistic combination of light excitation and ultrasound detection to empower biological and clinical investigations with rich optical contrast while effectively bridging the gap between micro and macroscopic imaging realms. State‐of‐the‐art OA embodiments consistently provide images at micron‐scale resolution through superficial tissue layers by means of focused illumination that can be smoothly exchanged for acoustic‐resolution images at diffuse light depths of several millimetres to centimetres via ultrasound beamforming or tomographic reconstruction. Taken together, this unique multi‐scale imaging capacity opens unprecedented capabilities for high‐resolution in vivo interrogations of the skin at scalable depths. Moreover, diverse anatomical and functional information is retrieved via dynamic mapping of endogenous chromophores such as haemoglobin, melanin, lipids, collagen, water and others. This, along with the use of non‐ionizing radiation, facilitates a clinical translation of the OA modalities. We review recent progress in OA imaging of the skin in preclinical and clinical studies exploiting the rich contrast provided by endogenous substances in tissues. The imaging capabilities of existing approaches are discussed in the context of initial translational studies on skin cancer, inflammatory skin diseases, wounds and other conditions.