Luis Menandez-Arias, Pierre Chatelain, Bernard MasereelTechnologies focusing on the direct modulation of protein activity, such as chromophore-assisted laser inactivation, provide a complementary approach to gene knockout and other validation techniques targeting gene expression. Protein inactivation techniques show high spatial and temporal resolution and can be used to validate novel targets (i.e. a single domain of a protein), missed by other inactivation strategies. This review was selected because protein inactivation technologies are expected to play a key role in the development of functional proteomics, through the identification of multiple interactions between gene products, and addressing the role of proteins in complex cellular pathways.