Recently, tissue-clearing techniques have made remarkable progress and now provide great opportunities to microscopists for exploring large biological samples. Clearing techniques tremendously increase animal tissues transparency and can, in some cases, make organs fully transparent. This has made possible high-resolution imaging and 3D visualization of large biological specimens exceeding 1 mm in size, including adult zebrafish. In this workshop, we propose a first part dedicated to the presentation of the main clearing techniques with a special focus on the zebrafish model. In a second part, we will demonstrate the benefit of clearing for 3D imaging of zebrafish specimens with a confocal/2-photon fluorescent microscope. We will also present the benefit of combining a vibratome to a confocal laser-scanning microscope (VibMicTM, Leica), which enables automated serial block-face imaging. Such hybrid system even allows imaging of larger specimens (i.e. up to several millimeters).