1. Karl Landsteiner discovered the three main blood groups (A, B, and O) in the early 1900s which helped explain inconsistent outcomes in blood transfusions. 2. Landsteiner found that red blood cells have antigens (A or B) on their surface, and the matching plasma contains antibodies (anti-A or anti-B) that cause agglutination if mismatched blood is transfused. 3. Understanding a person's blood group allows safe blood transfusions by only transfusing blood without antigens that would agglutinate the recipient's blood. This discovery revolutionized transfusion medicine.