Infrared (IR) spectroscopy has made important contributions to the arena of hematology in the past decade. The normal physiology and pathologic modifications of the three cellular elements in blood, i.e., leukocytes, erythrocytes and platelets, have been thoroughly investigated by this recently emerged optical tool. By revealing subtle alterations in the structures of macromolecules in these blood cells, IR spectroscopy has become an ideal complementary analytical tool to conventional biochemical assays used to diagnose various common hematological disorders. Such traditional assays include molecular structure measurements that determine erythrocyte membrane fluidity and conformational changes, lipid profiling of platelet membranes, as well as assays of leukocyte proliferation and differentiation. IR spectroscopic-based techniques can be used to analyze DNA alterations, secondary structural changes in proteins, and to profile cellular lipids. From a molecular and biomedical perspective, IR spectroscopy has been explored for the diagnosis and prognosis of leukemia and beta-thalassemia, to predict drug sensitivity and resistance in chemotherapy patients, and more recently to examine apoptotic processes in blood cells. These studies have shown great promise in the early identification of drug-resistant patients and the early diagnosis of hematological disorders, especially malignancies. Furthermore, IR spectroscopic-based investigations will enable specific mechanisms underlying hematological disorders to be elucidated by revealing the molecular changes in the blood cells at a very early pathogenesis stage.