Autoimmune hemolytic anemias (AIHAs) are conditions where autoantibodies target red blood cells (RBCs), leading to their destruction. AIHAs can be primary (unknown cause) or secondary (associated with diseases or infections). They are classified based on the direct antiglobulin test (DAT), which identifies the type of autoantibodies involved. The main categories include warm-antibody AIHA (wAIHA), cold-antibody AIHA (including cold agglutinin syndrome and disease), mixed AIHA, paroxysmal cold hemoglobinuria (PCH), DAT-negative AIHA, drug-induced AIHA, and passenger lymphocyte syndrome. wAIHA is the most common, characterized by IgG autoantibodies reacting at body temperature. Cold-antibody AIHA involves IgM antibodies active at lower temperatures, leading to complement activation. Mixed AIHA combines both IgG and IgM antibodies. PCH is a rare condition with IgG antibodies that activate complement upon warming. DAT-negative AIHA is managed like wAIHA. Drug-induced AIHA resembles wAIHA and may resolve after stopping the drug. Passenger lymphocyte syndrome occurs post-transplantation and is caused by donor B-cells producing antibodies against recipient RBCs. Diagnosis relies on DAT and other serological tests. Treatment varies by type, with glucocorticoids, IVIG, monoclonal antibodies, and complement inhibitors being common options. AIHA management requires personalized approaches, considering the patient's specific condition and response to therapy. New therapies, including monoclonal antibodies and complement inhibitors, are being explored to improve outcomes. Understanding the pathophysiology and classification of AIHAs is essential for effective diagnosis and treatment.Autoimmune hemolytic anemias (AIHAs) are conditions where autoantibodies target red blood cells (RBCs), leading to their destruction. AIHAs can be primary (unknown cause) or secondary (associated with diseases or infections). They are classified based on the direct antiglobulin test (DAT), which identifies the type of autoantibodies involved. The main categories include warm-antibody AIHA (wAIHA), cold-antibody AIHA (including cold agglutinin syndrome and disease), mixed AIHA, paroxysmal cold hemoglobinuria (PCH), DAT-negative AIHA, drug-induced AIHA, and passenger lymphocyte syndrome. wAIHA is the most common, characterized by IgG autoantibodies reacting at body temperature. Cold-antibody AIHA involves IgM antibodies active at lower temperatures, leading to complement activation. Mixed AIHA combines both IgG and IgM antibodies. PCH is a rare condition with IgG antibodies that activate complement upon warming. DAT-negative AIHA is managed like wAIHA. Drug-induced AIHA resembles wAIHA and may resolve after stopping the drug. Passenger lymphocyte syndrome occurs post-transplantation and is caused by donor B-cells producing antibodies against recipient RBCs. Diagnosis relies on DAT and other serological tests. Treatment varies by type, with glucocorticoids, IVIG, monoclonal antibodies, and complement inhibitors being common options. AIHA management requires personalized approaches, considering the patient's specific condition and response to therapy. New therapies, including monoclonal antibodies and complement inhibitors, are being explored to improve outcomes. Understanding the pathophysiology and classification of AIHAs is essential for effective diagnosis and treatment.