The exponential growth of protein sequence databases has increasingly made the fundamental question of searching for homologs a computational bottleneck. The amount of unique data, however, is not growing nearly as fast, we can exploit this fact to greatly accelerate homology search. Acceleration of programs in the popular PSI/DELTA-BLAST family of tools will not only speed-up homology search directly but also the huge collection of other current programs that primarily interact with large protein databases via precisely these tools.