Visualizing whole tissues and organs, at the single-cell level using three-dimensional (3D) optical imaging, remains a significant challenge in biology today. Due to tissue opacity caused by light scattering and absorption, optical sectioning techniques are unable to reach deep tissue layers, preventing the full 3D structure from being revealed. Tissue clearing methods, which induce transparency, enhance these optical imaging techniques, allowing for deeper image acquisition and analysis of large-scale tissue samples and organs. This chapter first describes the principles of tissue clearing and the steps required to achieve effective clearing. We then provide a list of existing methods categorized by their effects on tissue components and the refractive index and present the main optical sectioning techniques used to image tissues post-clearing. Additionally, we discuss various applications of organ clearing approaches for imaging, including examples involving tumors and multicellular spheroids. Particularly, we focused on advantages of clearing to visualize modifications induced by electroporation in internal layers of spheroids such as molecule penetration. Finally, we address technical issues and their solutions to achieve effective clearing, considering organ specificity and the desired level of resolution. Overall, this chapter aims to provide comprehensive knowledge of the existing clearing methods to enable new insights into the structure and function of the entire organs at high resolution.