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Currently available optical microscopic imaging techniques-confocal microscopy, multi-photon (also referred to as two-photon) microscopy, and optical coherence tomography-have revolutionized biological and medical research, based on strong optical contrast and high spatial resolution. Unfortunately, owing to unavoidable strong light scattering in biological tissues, such methods cannot maintain contrast and spatial resolution beyond one optical transport mean free path ( ~ 1 mm in tissues). Although model-based diffuse optical tomography is able to operate at greater depths, this technique fails to maintain spatial resolution. Photoacoustic tomography overcomes the fundamental penetration depth problem and achieves high-resolution optical imaging in deep tissues by combing light and ultrasound. In this review article, the multimodal imaging capability of photoacoustic tomography, integrated with existing imaging tools, is contemplated and the potential preclinical and clinical impacts of the combined systems are discussed.