Fluoroquinolones, a class of antibiotics that inhibit bacterial DNA synthesis by targeting topoisomerase IV and DNA gyrase, are widely used to treat bacterial infections. However, their use has led to increased microbial resistance and significant side effects, including neurological, cardiovascular, musculoskeletal, and endocrine issues. Neurological complications include encephalopathy, psychosis, seizures, peripheral neuropathy, and exacerbation of myasthenia gravis. Cardiovascular risks involve aortic aneurysm, dissection, and QT interval prolongation. Musculoskeletal effects include tendinopathy, ligament damage, and cartilage injury. Additionally, fluoroquinolones may cause hypoglycemia. These side effects are exacerbated by pre-existing conditions, concurrent medications, and the drug's ability to cross the blood-brain barrier. Despite their effectiveness, the risks and reduced efficacy due to resistance have led to recommendations for limited use, especially in vulnerable populations. The FDA has issued warnings about the severe risks associated with fluoroquinolones, emphasizing the need for careful consideration and alternative treatments when available. The review highlights the importance of understanding the mechanisms of these side effects to balance the benefits and risks of fluoroquinolone therapy.Fluoroquinolones, a class of antibiotics that inhibit bacterial DNA synthesis by targeting topoisomerase IV and DNA gyrase, are widely used to treat bacterial infections. However, their use has led to increased microbial resistance and significant side effects, including neurological, cardiovascular, musculoskeletal, and endocrine issues. Neurological complications include encephalopathy, psychosis, seizures, peripheral neuropathy, and exacerbation of myasthenia gravis. Cardiovascular risks involve aortic aneurysm, dissection, and QT interval prolongation. Musculoskeletal effects include tendinopathy, ligament damage, and cartilage injury. Additionally, fluoroquinolones may cause hypoglycemia. These side effects are exacerbated by pre-existing conditions, concurrent medications, and the drug's ability to cross the blood-brain barrier. Despite their effectiveness, the risks and reduced efficacy due to resistance have led to recommendations for limited use, especially in vulnerable populations. The FDA has issued warnings about the severe risks associated with fluoroquinolones, emphasizing the need for careful consideration and alternative treatments when available. The review highlights the importance of understanding the mechanisms of these side effects to balance the benefits and risks of fluoroquinolone therapy.