A family of small, noncoding RNAs, known as microRNAs, has recently emerged as sequence-specific regulators of gene expression. Hundreds of microRNAs have been identified in almost all metazoans genomes, but they are only beginning to be classified by functional roles. Here, we review microRNAs that have been shown to play roles in two closely related processes, lifespan and metabolic regulation. Understanding the metabolic and lifespan regulatory roles of these novel gene regulators will undoubtedly further our understanding of the complex genetic networks that control lifespan and metabolism, and will also provide us with novel targets for the therapeutic intervention of metabolic and age-related diseases.