Liquid CO2 is a viable alternative for the toxic and environmentally harmful solvents traditionally used in dry-cleaning industry. Although liquid CO2 dry-cleaning is being applied already at a commercial scale, it is still a relatively young technique which poses many challenges. The focus of this review is on the causes of the existing problems and directions to solve them. After presenting an overview of the state-of-the-art, we analyze the detergency challenges from the fundamentals of colloid and interface science. The properties of liquid CO2 such as dielectric constant, density, Hamaker constant, refractive index, viscosity and surface tension are presented and in the subsequent chapters their effects on CO2 dry-cleaning operation are delineated. We show, based on theory, that the van der Waals forces between a model soil (silica) and model fabric (cellulose) through liquid CO2 are much stronger compared to those across water or the traditional dry-cleaning solvent PERC (perchloroethylene). Prevention of soil particle redeposition in liquid CO2 by electrostatic stabilization is challenging and the possibility of using electrolytes having large anionic parts is discussed. Furthermore, the role of different additives used in dry-cleaning, such as water, alcohol and surfactants, is reviewed. Water is not only used as an aid to remove polar soils, but also enhances adhesion between fabric and soil by forming capillary bridges. Its role as a minor component in liquid CO2 is complex as it depends on many factors, such as the chemical nature of fabrics and soil, and also on the state of water itself, whether present as molecular solution in liquid CO2 or phase separated droplets. The phenomena of wicking and wetting in liquid CO2 systems are predicted from the Washburn–Lucas equation for fabrics of various surface energies and pore sizes. It is shown that nearly complete wetting is desirable for good detergency. The effect of mechanical action and fluid dynamic conditions on dry-cleaning is analyzed theoretically. From this it follows that in liquid CO2 an order of magnitude higher Reynold's number is required to exceed the binding forces between fabric and soil as opposed to PERC or water, mainly due to the strong van der Waals forces and the low viscosity of CO2 at dry-cleaning operational conditions.