Covering: Up to 2019 Phylogenetic methods become increasingly important in natural product research. The growing amount of genetic data available today is enabling us to infer the evolutionary history of secondary metabolite gene clusters and their encoded compounds. We are starting to understand patterns and mechanisms of how the enormous diversity of chemical compounds produced by nature has evolved and are able to use phylogenetic inference to facilitate functional predictions of involved enzymes. In this review, we highlight how phylogenetic methods can aid natural product discovery and predictions and demonstrate several examples how these have been used in the past. We are featuring a number of easy to use tools that aid tree building and analysis and are providing a short overview how to create and interpret a phylogenetic tree.