Comparative analysis of archaeal, bacterial, and eukaryotic genomes indicates the occurrence of horizontal gene transfer (HGT) in many genomes. Although widely studied in prokaryotic systems, eukaryotes, which were thought to evolve principally through reproduction and mutation (vertical gene transfer), also acquire novel genes and pathways through the acquisition of sequences from distantly related species. HGT is a notable phenomenon that allows the sharing of genetic information among members of most or all kingdoms. HGT leads to extremely dynamic genomes, which have the potential to effectively change the type and presence of secondary metabolites in an organism. HGT is documented in fungi, bacteria, animals, and plants - when viral mechanisms are included, all organisms likely are subject to HGT. The quantities of genetic material that are horizontally transferred range from small gene fragments to groups of genes, including whole operons that encode complex biochemical pathways. Examples of HGT that contribute to novel or expanded ranges of secondary metabolite products include filamentous and unicellular fungi, actinomycetes and other bacteria, and plants. In this chapter we will discuss several examples of secondary metabolite production that occur as a consequence of HGT, the study of natural products acquired through HGT processes and the ramifications of HGT for biosynthesis and exploitation of natural products that arise from horizontallytransferred pathways. We have focused primarily on the literature published from 2000 to 2015.