Examination of tissue histology by fluorescent microscopy is a fundamental tool for investigating the structure and function of organs in disease and health states. The traditional techniques of tissue sectioning, imaging, and analysis of sections are mostly incomplete and time consuming; hence, they present major limitations for obtaining a complete three-dimensional (3D) picture of biological systems. In recent years, tissue clearing and subsequent imaging of intact transparent organs have offered a substantial solution. Particularly, 3D imaging of solvent-cleared organs or 3DISCO emerged as a highly reproducible and straightforward method that is applicable to diverse tissues, including brain, spinal cord, lungs, immune organs, and tumors. The tissue clearing procedure can be completed in as short a period of time as 3 hr, and imaging can be completed as quickly as 45 min. Hence, 3DISCO is a powerful technique that offers 3D views of intact organs at a fraction of the time and labor required to complete standard histology studies.