This review discusses the distinction between lactose intolerance (LI) and cow's milk allergy (CMA) in infants, two common adverse reactions to cow's milk. LI is due to insufficient lactase activity, leading to undigested lactose causing gastrointestinal symptoms, while CMA is an immune response to cow's milk proteins, particularly casein or β-lactoglobulin. Both conditions present with similar symptoms, leading to potential misdiagnosis. Proper diagnosis is crucial to avoid inappropriate dietary restrictions and ensure adequate nutrition. LI is managed with lactose-free formulas, whereas CMA requires formulas with hydrolyzed proteins or amino acids. The review emphasizes the importance of understanding the pathophysiology and clinical differences between LI and CMA to guide accurate diagnosis and treatment in infants.This review discusses the distinction between lactose intolerance (LI) and cow's milk allergy (CMA) in infants, two common adverse reactions to cow's milk. LI is due to insufficient lactase activity, leading to undigested lactose causing gastrointestinal symptoms, while CMA is an immune response to cow's milk proteins, particularly casein or β-lactoglobulin. Both conditions present with similar symptoms, leading to potential misdiagnosis. Proper diagnosis is crucial to avoid inappropriate dietary restrictions and ensure adequate nutrition. LI is managed with lactose-free formulas, whereas CMA requires formulas with hydrolyzed proteins or amino acids. The review emphasizes the importance of understanding the pathophysiology and clinical differences between LI and CMA to guide accurate diagnosis and treatment in infants.