Copper is an essential trace element for eukaryotes, playing a crucial role in redox reactions and cellular processes. However, its toxicity can lead to severe cellular damage, particularly in conditions like Wilson's disease, where the copper transporter ATP7B is malfunctioning. This review discusses the mechanisms and cellular targets of toxic excess copper, focusing on acute and chronic copper intoxication. **Systemic Copper Distribution:** Copper is primarily absorbed in the small intestine and distributed to various organs, with the liver being the key organ for excretion. Copper is transported by copper transporters like CTR1 and ATP7B, and chaperoned by proteins like Atox1 and ATP7A. ATP7A and ATP7B play critical roles in regulating intracellular copper homeostasis, with ATP7B being highly expressed in the liver. **Cellular Copper Turnover:** Copper is essential for redox enzymes and is tightly regulated to prevent toxicity. Copper is taken up by DMT1 and reduced by reductases before being delivered to the TGN by CTR1. Atox1 and ATP7B then transport copper to mitochondria and other cellular compartments, where it is used in various enzymes and proteins. **Mechanisms of Copper Toxicity:** 1. **Oxidative Stress:** While often considered the primary cause, oxidative stress may emerge as a late consequence of overwhelmed defense mechanisms rather than the main driver of toxicity. 2. **Cuproptosis:** This is a novel form of cell death characterized by mitochondrial copper accumulation and proteotoxic stress, potentially linked to cancer therapy. 3. **Protein Toxicity:** Copper can directly inhibit bacterial enzymes and damage proteins, particularly in the mitochondrial compartment. 4. **Nuclear Receptor Signaling:** Copper affects transcriptional regulation by interfering with zinc finger-based transcriptional regulators, particularly nuclear receptors. 5. **Interference with Intracellular Signaling:** Copper modulates various signaling pathways, affecting processes like brain-derived neurotropic factor signaling and epidermal growth factor receptor activation. 6. **Zinc-Dependent Enzymes:** Copper can displace zinc from zinc-dependent enzymes, inhibiting their function. 7. **Interference with Iron Homeostasis:** Copper and iron metabolic pathways are intertwined, and copper excess can inhibit iron absorption and mobilization. **Targets of Copper Toxicity:** 1. **Mitochondrial Copper Toxicity:** Mitochondria are early targets of increased copper intake, leading to structural and functional defects. 2. **Inhibition of Autophagy and Mitophagy:** Copper can induce autophagy but also impair lysosomal activity, affecting cellular renewal. 3. **Target Sites in the Central Nervous System:** Astrocytes and neurons are particularly vulnerable to copper toxicity, with astrocytes providing protective GSH and MTs. **Acute Copper Intoxication:** Acute copper toxicity results from accidental ingestion or suicideCopper is an essential trace element for eukaryotes, playing a crucial role in redox reactions and cellular processes. However, its toxicity can lead to severe cellular damage, particularly in conditions like Wilson's disease, where the copper transporter ATP7B is malfunctioning. This review discusses the mechanisms and cellular targets of toxic excess copper, focusing on acute and chronic copper intoxication. **Systemic Copper Distribution:** Copper is primarily absorbed in the small intestine and distributed to various organs, with the liver being the key organ for excretion. Copper is transported by copper transporters like CTR1 and ATP7B, and chaperoned by proteins like Atox1 and ATP7A. ATP7A and ATP7B play critical roles in regulating intracellular copper homeostasis, with ATP7B being highly expressed in the liver. **Cellular Copper Turnover:** Copper is essential for redox enzymes and is tightly regulated to prevent toxicity. Copper is taken up by DMT1 and reduced by reductases before being delivered to the TGN by CTR1. Atox1 and ATP7B then transport copper to mitochondria and other cellular compartments, where it is used in various enzymes and proteins. **Mechanisms of Copper Toxicity:** 1. **Oxidative Stress:** While often considered the primary cause, oxidative stress may emerge as a late consequence of overwhelmed defense mechanisms rather than the main driver of toxicity. 2. **Cuproptosis:** This is a novel form of cell death characterized by mitochondrial copper accumulation and proteotoxic stress, potentially linked to cancer therapy. 3. **Protein Toxicity:** Copper can directly inhibit bacterial enzymes and damage proteins, particularly in the mitochondrial compartment. 4. **Nuclear Receptor Signaling:** Copper affects transcriptional regulation by interfering with zinc finger-based transcriptional regulators, particularly nuclear receptors. 5. **Interference with Intracellular Signaling:** Copper modulates various signaling pathways, affecting processes like brain-derived neurotropic factor signaling and epidermal growth factor receptor activation. 6. **Zinc-Dependent Enzymes:** Copper can displace zinc from zinc-dependent enzymes, inhibiting their function. 7. **Interference with Iron Homeostasis:** Copper and iron metabolic pathways are intertwined, and copper excess can inhibit iron absorption and mobilization. **Targets of Copper Toxicity:** 1. **Mitochondrial Copper Toxicity:** Mitochondria are early targets of increased copper intake, leading to structural and functional defects. 2. **Inhibition of Autophagy and Mitophagy:** Copper can induce autophagy but also impair lysosomal activity, affecting cellular renewal. 3. **Target Sites in the Central Nervous System:** Astrocytes and neurons are particularly vulnerable to copper toxicity, with astrocytes providing protective GSH and MTs. **Acute Copper Intoxication:** Acute copper toxicity results from accidental ingestion or suicide