Discovery of regulatory motifs in unaligned DNA sequences remains a fundamental problem in computational biology. Two categories of algorithms have been developed to identify common motifs from a set of DNA sequences. The first can be called a multiple genes, single species approach. It proposes that a degenerate motif is embedded in some or all of the otherwise unrelated input sequences and tries to describe a consensus motif and identify its occurrences. It is often used for co-regulated genes identified through experimental approaches. The second approach can be called single gene, multiple species. It requires orthologous input sequences and tries to identify unusually well conserved regions by phylogenetic footprinting. Both approaches perform well, but each has some limitations. It is tempting to combine the knowledge of co-regulation among different genes and conservation among orthologous genes to improve our ability to identify motifs.