MotifCluster finds related motifs in a set of sequences, and clusters the sequences into families using the motifs they contain. MotifCluster, at http://bmf.colorado.edu/motifcluster, lets users test whether proteins are related, cluster sequences by shared conserved motifs, and visualize motifs mapped onto trees, sequences and three-dimensional structures. We demonstrate MotifCluster's accuracy using gold-standard protein superfamilies; using recommended settings, families were assigned to the correct superfamilies with 0.17% false positive and no false negative assignments.