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Hydrophobicity refers to the physical property of a molecule that does not associate with water. The word "hydrophobic" literally means "water-fearing". Substances that are hydrophobic tend to repel water. This phenomenon is often observed in the behavior of nonpolar molecules in polar solvents like water. For example, oil and water do not mix because oil is hydrophobic.

The underlying reason for hydrophobicity lies in the interactions between molecules. Water molecules are polar, meaning they have a partial positive charge on the hydrogen atoms and a partial negative charge on the oxygen atom. These partial charges allow water molecules to form hydrogen bonds with each other and with other polar molecules. Hydrophobic molecules, on the other hand, are typically nonpolar, lacking significant charge separation. When a hydrophobic molecule is introduced into water, it disrupts the hydrogen bonding network of water. To minimize this disruption and maximize their own entropy, water molecules tend to surround the hydrophobic molecule in a cage-like structure. This arrangement is energetically unfavorable, leading to the hydrophobic effect, where hydrophobic substances aggregate together to reduce their contact area with water.

Hydrophobicity plays a crucial role in many biological and chemical processes. In biology, the hydrophobic effect drives the folding of proteins, forming the hydrophobic core of the protein structure. It also dictates the structure of cell membranes, where the hydrophobic tails of lipids are sequestered away from the aqueous environment. In chemistry, hydrophobicity is a key factor in designing surfactants, which have both hydrophobic and hydrophilic parts, allowing them to bridge the interface between oil and water. Understanding and manipulating hydrophobicity is essential in fields ranging from materials science to drug discovery.