Cation–π interactions play an important role in biomolecular recognition and have been shown to involve all major classes of biomolecules. However, unlike other interactions such as salt bridges, hydrogen bonding, and the hydrophobic effect, major advances in establishing their prevalence in biology are more recent. This review first provides a brief discussion of the nature of cation–π interactions as determined from model systems, followed by examples of cation–π interactions in proteins, nucleic acids, and lipids. This body of work clearly demonstrates the ubiquitous and consequential nature of cation–π interactions in biomolecular recognition.