THESEUS, the ZIB threading environment, is a parallel implementation of a protein threading based on a multi-queued Branch-and-Bound optimal search algorithm to find the best sequence-to-structure alignment through a library of template structures. THESEUS uses a template core model based on secondary structure definition and a scoring function based on knowledge-based potentials reflecting pairwise interactions and the chemical environment, as well as pseudo-energies for homology detection, loop alignment, and secondary structure matching. The threading core is implemented in C++ as a SPMD parallelization architecture using MPI for communication. The environment is designed for generic testing of different scoring functions and search algorithms. A validation of the structure prediction results has been done on the basis of standard threading benchmark sets. THESEUS successfully participated in the 6th Critical Assessment of Techniques for Protein Structure Prediction (CASP).