AMPK regulates the circadian clock by phosphorylating and degrading cryptochrome 1 (CRY1). In mouse fibroblasts, AMPK phosphorylates and destabilizes CRY1, which is involved in circadian rhythms. In mouse livers, AMPK activity and nuclear localization are rhythmic and inversely correlated with CRY1 abundance. AMPK stimulation destabilizes cryptochromes and alters circadian rhythms. Mice with disrupted AMPK pathways show altered peripheral clocks. Phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in peripheral organs. The mammalian circadian clock is regulated by alternating actions of activators and repressors of transcription. CRY1 and CRY2 proteins inhibit CLOCK and BMAL1, leading to rhythmic expression. Post-translational modifications, including ubiquitination of CRY1 by FBXL3, are required for resetting the clock. AMPK phosphorylates CRY1 at specific sites, altering its stability. Mutation of these sites affects CRY1 stability and interaction with FBXL3 and PER2. AMPK directly phosphorylates CRY1 in vitro. In vivo, AMPK phosphorylates CRY1 at S71, which is mediated by AMPK. AMPK activity is regulated by glucose availability and affects CRY1 stability. AMPK activation reduces CRY1 levels, leading to de-repression of CLOCK:BMAL1 targets. Glucose deprivation activates AMPK and reduces CRY1 stability, leading to de-repression of CLOCK:BMAL1 targets. AMPK activity is rhythmic in mouse livers, with phosphorylation of AMPK substrates peaking during the day. AMPKβ2 subunit expression is circadian, and its oscillation may regulate AMPK nuclear import. AMPK nuclear localization peaks synchronously with AMPKβ2 expression, coinciding with minimum nuclear CRY1. AMPK activation reduces CRY1 levels, stabilizing cryptochromes and disrupting circadian rhythms. AMPK is a central regulator of metabolic processes and its rhythmic regulation has implications for circadian metabolism. Genetic alteration of circadian clocks affects feeding behavior, body weight, and glucose homeostasis, which are also altered by AMPK manipulation. AMPK-mediated circadian regulation and CRY1 as a chemical energy sensor suggest a close relationship between metabolic and circadian rhythms.AMPK regulates the circadian clock by phosphorylating and degrading cryptochrome 1 (CRY1). In mouse fibroblasts, AMPK phosphorylates and destabilizes CRY1, which is involved in circadian rhythms. In mouse livers, AMPK activity and nuclear localization are rhythmic and inversely correlated with CRY1 abundance. AMPK stimulation destabilizes cryptochromes and alters circadian rhythms. Mice with disrupted AMPK pathways show altered peripheral clocks. Phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in peripheral organs. The mammalian circadian clock is regulated by alternating actions of activators and repressors of transcription. CRY1 and CRY2 proteins inhibit CLOCK and BMAL1, leading to rhythmic expression. Post-translational modifications, including ubiquitination of CRY1 by FBXL3, are required for resetting the clock. AMPK phosphorylates CRY1 at specific sites, altering its stability. Mutation of these sites affects CRY1 stability and interaction with FBXL3 and PER2. AMPK directly phosphorylates CRY1 in vitro. In vivo, AMPK phosphorylates CRY1 at S71, which is mediated by AMPK. AMPK activity is regulated by glucose availability and affects CRY1 stability. AMPK activation reduces CRY1 levels, leading to de-repression of CLOCK:BMAL1 targets. Glucose deprivation activates AMPK and reduces CRY1 stability, leading to de-repression of CLOCK:BMAL1 targets. AMPK activity is rhythmic in mouse livers, with phosphorylation of AMPK substrates peaking during the day. AMPKβ2 subunit expression is circadian, and its oscillation may regulate AMPK nuclear import. AMPK nuclear localization peaks synchronously with AMPKβ2 expression, coinciding with minimum nuclear CRY1. AMPK activation reduces CRY1 levels, stabilizing cryptochromes and disrupting circadian rhythms. AMPK is a central regulator of metabolic processes and its rhythmic regulation has implications for circadian metabolism. Genetic alteration of circadian clocks affects feeding behavior, body weight, and glucose homeostasis, which are also altered by AMPK manipulation. AMPK-mediated circadian regulation and CRY1 as a chemical energy sensor suggest a close relationship between metabolic and circadian rhythms.