A brief description of tissue optics, concept of ‘tissue optical windows’ and method of optical clearing (OC) based on controllable and reversible modification of tissue optical properties by their impregnation with a biocompatible optical clearing agent (OCA) will be done. Fundamentals and major mechanisms of OC allowing one to enhance optical imaging facilities and laser treatment efficiency of living tissues will be presented. The enhancement of probing/treatment depth and image contrast for a number of human and animal tissues investigated by using different optical modalities, including diffuse reflectance spectroscopy, collimated transmittance, OCT, photoacoustic microscopy, linear and nonlinear fluorescence, SHG and Raman microscopies will be discussed. Experimental data on the diffusion and permeability coefficients of biocompatible FDA approved OCAs, such as glucose, glycerol, PEG, albumin, CT contrast agents (Iohexol (OmnipaqueTM) and Iodixanol (VisipaqueTM)), and MRI contrast agents (Gadobutrol (GadovistTM)) in normal and pathological tissues (cancer and diabetes) will be presented. Perspectives of immersion optical clearing/contrasting technique aiming to enhance imaging of living tissues by using different imaging modalities working in the ultra-broad wavelength range will be discussed.