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Metallic nanoparticles (NP) have been used for biomedical applications especially for imaging. Compared to nonmetallic NP, metallic NP provide high contrast images because of their optical light scattering, magnetic resonance, X-ray absorption, or other physicochemical properties. In this review, a series of in vitro imaging techniques for metallic NP will be introduced, meanwhile their strengths and weaknesses will be discussed. By utilizing these imaging methods, the cellular uptake of metallic NP can be easily visualized to better understand the endocytic mechanisms of NP intracellular delivery. Several types of metallic NP that are used for imaging or as contrast agents such as quantum dots, gold, iron oxide, and other metallic NP will be presented. Cellular uptake of metallic NP and associated endocytic mechanisms highly depends upon the NP size, charge, surface coating, shape, or other factors such as cell type, cell differentiation status, cell surface status, external forces, protein binding, temperature, and the biological milieu. Classical endocytic routes such as lipid raft-mediated pathways, clathrin or caveolae-mediated pathways, macropinocytosis, and phagocytosis have been investigated, yet there is still a demand to determine other endocytic pathways. Knowing the different methodologies used to determine the endocytic pathways will increase the understanding of NP toxicity, cancer cell targeting, and imaging, so that surface coatings can be created for efficient cell uptake of metallic NP with minimal cytotoxicity WIREs Nanomed Nanobiotechnol 2017, 9:e1419. doi: 10.1002/wnan.1419 For further resources related to this article, please visit the WIREs website.