Derek Lowe writes about the "hot" field of activity-based protein profiling, which he explains via a critique of a current paper out of Benjamin Cravatt's lab at Scripps. His paper tested the most effective ways to photoaffinity-label histone deacetylase enzymes and found that in vitro and in vivo results are not always the same. Lowe emphasizes that in drug discovery especially, assumptions should never be made.