Haptoglobin (HP) is a liver glycoprotein that is actively synthesized during inflammatory and hemolytic processes. It also has pro-oxidant and proinflammatory properties, which are a function of its genotype. The genetic polymorphism of the chains leads to synthesis of three phenotypes/proteins, which are related to the number and type of chains and their molecular weight, namely HP1-1, HP1-2 and HP2-2. Patients with HP2-2 have more vascular complications, while those with HP1-1 have fewer. HP is involved in the worsening of diseases, such as HP2-2 in aggravation of vaso-occlusive crises in sickle cell disease, and worsening of the pathophysiology of other diseases. In contrast, HP1-1 confers better protection against diseases. All of this suggests that further studies should be conducted, including experimental and analytical studies focused on demonstrating the influence of different HP genotypes on individual clinical and hematological data. This would help in understanding the role played by this genetic polymorphism in the pathophysiology of diseases.