Lysine acetylation, first identified in histones, was initially thought to be a posttranslational modification occuring only in eukaryotic cells that controlled gene transcription either via remodeling chromatin or altering the transcriptional machinery. Recent studies, however, have shown that acetylation is a well-conserved metabolic regulatory mechanism that plays critical roles in regulating and coordinating cell metabolism. Acetylation regulates metabolism through controlling gene transcription, altering the metabolic enzymes activity and possibly other functional aspects, of metabolic enzymes. In this review, we provide an overview of the roles and significance of acetylation in metabolic regulation.