A substance tends to dissolve in solvents that are chemically similar to it.

Nonpolar substances such as lipids do not dissolve in water because their molecules in solution would prevent water molecules from forming as many hydrogen bonds as in pure water. A polar substance such as a sugar is soluble in water because the decrease in the number of water-water bonds is compensated by the formulation of strong hydrogen bonds between the water molecules and the hydrogen bonds of the sugar.

The solubility properties of a biological substance will generally be one of its most important characteristics. Solubility determines which substances can pass directly through the nonpolar interior of the cell membrane (i.e. steroid hormones) and which substances require a channel (ions and sugars).