Metabolic gene clusters (MGCs) have provided some of the earliest glimpses at the biochemical machinery of yeast and filamentous fungi. MGCs encode diverse genetic mechanisms for nutrient acquisition and the synthesis/degradation of essential and adaptive metabolites. Beyond encoding the enzymes performing these discrete anabolic or catabolic processes, MGCs may encode a range of mechanisms that enable their persistence as genetic consortia; these include enzymatic mechanisms to protect their host fungi from their inherent toxicities, and integrated regulatory machinery. This modular, self-contained nature of MGCs contributes to the metabolic and ecological adaptability of fungi. The phylogenetic and ecological patterns of MGC distribution reflect the broad diversity of fungal life cycles and nutritional modes. While the origins of most gene clusters are enigmatic, MGCs are thought to be born into a genome through gene duplication, relocation, or horizontal transfer, and analyzing the death and decay of gene clusters provides clues about the mechanisms selecting for their assembly. Gene clustering may provide inherent fitness advantages through metabolic efficiency and specialization, but experimental evidence for this is currently limited. The identification and characterization of gene clusters will continue to be powerful tools for elucidating fungal metabolism as well as understanding the physiology and ecology of fungi.