Up to 5% of the genomes of euascomycete fungi are occupied by gene clusters that encode biochemical pathways for a diversity of polyketides, non-ribosomal peptides, alkaloids, terpenoids, and combinations of these building blocks, to produce an array of mycotoxins that poison animals (e.g. cyclosporin, lovastatin, fumonisin), phytotoxins that act as pathogenicty factors on plants (e.g T-toxin, AAL-toxin, HC-toxin), and antibacterials that deter their bacterial competitors (e.g. penicillin). Genomic comparisons show that all euascomycete fungi, regardless of nutritional mode (plant or animal pathogen, endophyte, or saprobe) share the same classes of secondary metabolite genes. Therefore, this genetic legacy has been used by diverging lineages of fungi for diverse biotic interactions as they evolved to occupy new niches. Among the questions we trying to answer are: how does the expansion of gene families occur? What are the relative roles of gene loss cf. horizontal gene transfer? How do novel metabolic pathways form? Why do the constituent genes of each pathway occur in gene clusters, whereas other functionally related genes are scattered throughout the genome of a eukaryotic organism?