The photoactivatable aryl ketone derivatives have been rediscovered as biochemical probes in the last 5 years. The expanding use of benzophenone (BP) photoprobes can be attributed to three distinct chemical and biochemical advantages. First, BPs are chemically more stable than diazo esters, aryl azides, and diazirines. Second, BPs can be manipulated in ambient light and can be activated at 350-360 nm, avoiding protein-damaging wavelengths. Third, BPs react preferentially with unreactive C-H bonds, even in the presence of solvent water and bulk nucleophiles. These three properties combine to produce highly efficient covalent modifications of macromolecules, frequently with remarkable site specificity. This Perspectives includes a brief review of BP photochemistry and a selection of specific applications of these photoprobes, which address questions in protein, nucleic acid, and lipid biochemistry.