The founding editor was Emile Zuckerkandl, who remained editor-in-chief until the late 1990s.

[1][2] In a 1998 editorial, Zuckerkandl stated that he wanted the journal to "insure that this field be covered in its broadest sense" by publishing research that is of broad interest to the field of molecular evolution that it helped define, as well as to biology in general.

To this end, Zuckerkandl stated that the journal does not cover research either on practical applications of molecular evolution, or articles "whose focus is very restricted and that do not lead to valuable insights beyond their narrow topic".

[4] An editorial by Niles Lehman, editor-in-chief at the time, in 2013 stated a refocus of the journal's aims towards its original scope with the inclusion of an emphasis on the mechanisms of evolution.

"Studies performed using computational, chemical, in vitro, and experimental evolutionary methods, and those that target species-independent phenomena such as ribosomal function, genetic code evolution, and regulatory processes will occupy more of the journal space than before, with the consequence that work that is organism-, lineage-, or gene-specific will require a broader impact to be considered for publication.