Chloride, the most abundant extracellular anion, is vital for maintaining electroneutrality, acid-base balance, and neuromuscular function. It closely interacts with sodium and helps regulate osmolality and fluid balance. Corrected chloride concentrations, calculated using measured chloride and sodium concentrations, assist clinicians in distinguishing true chloride imbalances from changes caused by water balance alterations. In acid-base regulation, chloride has an inverse relationship with bicarbonate: hyperchloremia typically indicates metabolic acidosis, while hypochloremia suggests metabolic alkalosis. Recent studies in both humans and animals show that abnormal chloride levels are linked to increased morbidity and mortality, highlighting their clinical significance.