A key question in evolutionary developmental biology is how DNA sequence changes have directed the evolution of morphological diversity. The widely accepted view was that morphological changes resulted from differences in number and/or type of transcription factors, or even from small changes in the amino acid sequence of similar proteins. Research over the last two decades indicated that most of the developmental and genetic mechanisms that produce new structures involve proteins that are deeply conserved. These proteins are encoded by a type of genes known as 'toolkit' genes that control a plethora of processes essential for the correct development of the organism. Mutations in these toolkit genes produce deleterious pleiotropic effects. In contrast, alterations in regulatory regions affect their expression only at specific sites in the organism, facilitating morphological change at the tissue and organ levels. However, some examples from the animal and plant fields indicate that coding mutations also contributed to phenotypic evolution. Therefore, the main question at this point is to what extent these mechanisms have contributed to the evolution of morphological diversity. Today, an increasing amount of data, especially from the plant field, implies that changes in cis-regulatory sequences in fact played a major role in evolution. © 2014 The Author.