Iron-sulfur clusters are among the most ancient biological cofactors and are thought to have had an ancient role in mediating the chemical reactions that led to life. Two different, yet complementary approaches, based on bioinorganic chemistry and prebiotic chemistry, have already provided important clues for the formation and activity of biomimetic iron-sulfur analogues in aqueous solution. This frontier article discusses the efforts spent in the last 50 years in the context of peptide-coordinated iron-sulfur clusters, with a particular emphasis on insightful contributions from recent prebiotic chemistry research.