This review discusses the toxicity mechanisms of gadolinium (Gd) and gadolinium-based contrast agents (GBCAs), focusing on their potential renal toxicity. GBCAs have been used for over 30 years in magnetic resonance imaging (MRI) to enhance diagnostic accuracy. However, exposure to GBCAs can lead to Gd release and tissue deposition, causing short- and long-term toxicity in various organs, particularly the kidneys. The increasing prevalence of chronic kidney disease and the association of GBCA-related complications with renal dysfunction highlight the importance of understanding Gd toxicity mechanisms. Gd (III) toxicity is influenced by its chemical form and the structure of GBCAs. Linear GBCAs are more prone to Gd release compared to macrocyclic GBCAs, which have a more stable structure and lower Gd release. Gd (III) can cause oxidative stress, inflammation, and apoptosis, leading to tissue damage. It can also interfere with calcium homeostasis, mitochondrial function, and cellular processes, contributing to toxicity. Studies have shown that Gd (III) can accumulate in various organs, including the kidneys, brain, liver, skin, and bones. This accumulation is more pronounced in individuals with renal dysfunction, leading to conditions such as nephrogenic systemic fibrosis (NSF). The retention of Gd (III) in tissues can be exacerbated by impaired renal function, increasing the risk of long-term toxicity. The review highlights the differences in toxicity between linear and macrocyclic GBCAs. While macrocyclic GBCAs are generally considered safer, they can still cause Gd (III) retention in tissues. The use of macrocyclic GBCAs is recommended for patients with renal insufficiency, but further research is needed to fully understand their long-term effects. The review also discusses the potential for alternative agents with improved safety profiles, including macro- and supramolecular Gd (III) complexes. These agents may offer better targeting and reduced toxicity compared to traditional GBCAs. Additionally, the use of chelating agents and antioxidant therapies may help mitigate Gd (III) toxicity. In conclusion, the mechanisms of Gd (III) toxicity are complex and involve multiple pathways, including oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Understanding these mechanisms is crucial for developing safer contrast agents and improving the safety profile of GBCAs in clinical practice. Further research is needed to fully elucidate the long-term effects of GBCAs and to develop strategies to minimize their toxicity.This review discusses the toxicity mechanisms of gadolinium (Gd) and gadolinium-based contrast agents (GBCAs), focusing on their potential renal toxicity. GBCAs have been used for over 30 years in magnetic resonance imaging (MRI) to enhance diagnostic accuracy. However, exposure to GBCAs can lead to Gd release and tissue deposition, causing short- and long-term toxicity in various organs, particularly the kidneys. The increasing prevalence of chronic kidney disease and the association of GBCA-related complications with renal dysfunction highlight the importance of understanding Gd toxicity mechanisms. Gd (III) toxicity is influenced by its chemical form and the structure of GBCAs. Linear GBCAs are more prone to Gd release compared to macrocyclic GBCAs, which have a more stable structure and lower Gd release. Gd (III) can cause oxidative stress, inflammation, and apoptosis, leading to tissue damage. It can also interfere with calcium homeostasis, mitochondrial function, and cellular processes, contributing to toxicity. Studies have shown that Gd (III) can accumulate in various organs, including the kidneys, brain, liver, skin, and bones. This accumulation is more pronounced in individuals with renal dysfunction, leading to conditions such as nephrogenic systemic fibrosis (NSF). The retention of Gd (III) in tissues can be exacerbated by impaired renal function, increasing the risk of long-term toxicity. The review highlights the differences in toxicity between linear and macrocyclic GBCAs. While macrocyclic GBCAs are generally considered safer, they can still cause Gd (III) retention in tissues. The use of macrocyclic GBCAs is recommended for patients with renal insufficiency, but further research is needed to fully understand their long-term effects. The review also discusses the potential for alternative agents with improved safety profiles, including macro- and supramolecular Gd (III) complexes. These agents may offer better targeting and reduced toxicity compared to traditional GBCAs. Additionally, the use of chelating agents and antioxidant therapies may help mitigate Gd (III) toxicity. In conclusion, the mechanisms of Gd (III) toxicity are complex and involve multiple pathways, including oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Understanding these mechanisms is crucial for developing safer contrast agents and improving the safety profile of GBCAs in clinical practice. Further research is needed to fully elucidate the long-term effects of GBCAs and to develop strategies to minimize their toxicity.