This review deals with the general principles and problems of formaldehyde fixation. After a short description of 1) formaldehyde methods of production, 2) chemical properties of formaldehyde solution, and 3) kinetic of formaldehyde binding in tissue, formaldehyde reactivity with the tissue biopolymers, proteins and cucleic acids mainly, are described. Howformaldehyde fixation of tissues adversely affects the reactivity of cellular proteins with their respective specific antibody and the ways the most commonly used retrieval techniques in oct ore, thereafter, discussed. Finally, concerns that need to be dealt with when formalin-fixed specimens are used for genomic analysis and studies of DNA expression are highlighted.