Analyses of plant and microbial genome sequences have revealed many genes and gene clusters encoding proteins similar to those known to be involved in the biosynthesis of structurally-complex natural products. Many of these genes and gene clusters do not direct the production of known metabolites of the organism in which they are found. Others represent novel gene clusters that direct the biosynthesis of known natural products. This article highlights several examples of new biosynthetic chemistry discovered in the course of investigating such gene clusters.