Pin1 contains an N-terminal WW domain and a C-terminal peptidyl-prolyl cis-trans isomerase (PPIase) domain connected by a flexible linker. To address the energetic and structural basis for WW domain recognition of phosphoserine (P. Ser)/phosphothreonine (P. Thr)-proline containing proteins, we report the energetic and structural analysis of a Pin1–phosphopeptide complex. The X-ray crystal structure of Pin1 bound to a doubly phosphorylated peptide (Tyr-P. Ser-Pro-Thr-P. Ser-Pro-Ser) representing a heptad repeat of the RNA polymerase II large subunit's C-terminal domain (CTD), reveals the residues involved in the recognition of a single P. Ser side chain, the rings of two prolines, and the backbone of the CTD peptide. The side chains of neighboring Arg and Ser residues along with a backbone amide contribute to recognition of P. Ser. The lack of widespread conservation of the Arg and Ser residues responsible for P. Ser recognition in the WW domain family suggests that only a subset of WW domains can bind P. Ser-Pro in a similar fashion to that of Pin1.