The fourth EMBO-sponsored conference on Experimental Approaches to Evolution and Ecology Using Yeast and Other Model Systems (https://www.embl.de/training/events/2016/EAE16-01/), was held at the EMBL in Heidelberg, Germany, October 19-23, 2016. The conference was organized by Judith Berman (Tel Aviv University), Maitreya Dunham (University of Washington), Jun-Yi Leu (Academia Sinica), and Lars Steinmetz (EMBL Heidelberg and Stanford University). The meeting attracted ~120 researchers from 28 countries and covered a wide range of topics in the fields of genetics, evolutionary biology, and ecology with a unifying focus on yeast as a model system. Attendees enjoyed the Keith Haring inspired yeast florescence microscopy artwork (Figure 1), a unique feature of the meeting since its inception, and the one-minute flash talks that catalyzed discussions at two vibrant poster sessions. The meeting coincided with the 20th anniversary of the publication describing the sequence of the first eukaryotic genome, Saccharomyces cerevisiae (Goffeau et al. 1996). Many of the conference talks focused on important questions about what is contained in the genome, how genomes evolve, and the architecture and behavior of communities of phenotypically and genotypically diverse microorganisms. Here, we summarize highlights of the research talks around these themes. Nearly all presentations focused on novel findings, and we refer the reader to relevant manuscripts that have subsequently been published. Copyright © 2017, G3: Genes, Genomes, Genetics.