The quality of biospecimens is an important issue for clinical assays. These specimens contain various biomarkers, e.g., cells, proteins, nucleic acids, and phospholipids, most of which start to degrade just after sampling from patients. Because this degradation proceeds in a water-rich condition, under which water, as a solvent, dominates the degradation rate, the samples are often preserved at a low temperature in a frozen, lyophilized, or desiccated state to inhibit the motion of water molecules. However, frozen and/or desiccated water solutions surrounding the biomarkers markedly change the physicochemical environment, and can sometimes accelerate the degradation process. This physicochemical variation in water solutions includes dehydration by freezing or desiccation, osmotic stress by frozen-induced condensation, intra-/extracellular ice formation, and vitrification. This article provides an outline of such physicochemical variation in water solutions and its effects, especially on a fluid specimen, like a blood sample. The outline is composed of three parts after the introduction chapter: 1) general physicochemical changes in the water solution during freezing, frozen storage, and thawing, 2) damage of cells and proteins during freezing, frozen storage, and thawing, and 3) physicochemical changes of the water solution during desiccation and lyophilization and their effects on cells and proteins. As the mechanism of cellular damage is different from that of protein damage, they are discussed separately.