Members of the Whirly family of proteins are found throughout the plant kingdom and are predicted to share the ability to bind to single-stranded DNA. Arabidopsis and potato Whirly orthologs act as transcription factors that regulate defense gene expression; the Arabidopsis Whirly protein AtWhy1 contributes to both basal and specific defense responses. Analysis of the crystal structure of potato StWhy1 has provided insight into the DNA-binding mechanism of this family of proteins, their mode of action and possible autoregulation. There is evidence to suggest that Whirly proteins might play roles in processes other than defense responses and could function in the chloroplast as well as in the nucleus.