Tissues have to undergo through series of ‘tissue processing’ procedures before they are ready to be diagnosed under the microscope. The various steps of tissue processing include fixing, dehydration, clearing and infiltration. Clearing refers to the process of replacing the dehydrant with a substance that is miscible with the embedding medium. It is one of the most critical steps of tissue processing and largely affects the clarity of the final section and hence the precision of diagnosis. Since time immemorial, xylene has been the non-substitutable clearing agent used in histology laboratories. However, off late, xylene has been found to have many toxic effects. This review aims to discusses the properties and toxic effects of xylene, merits and demerits of the other commonly used clearing agents and also critically analyses the various suggested substitutes of xylene.