This chapter discusses the red blood cells in detail including the structure hematopoiesis and destruction. Second part of chapter discuses the hemoglobin structure and its formation. The hematocrit (HCT) or packed cell volume (PCV) or erythrocyte volume fraction (EVF) is the ratio of the volume of erythrocytes to that of the whole blood and is reported as percentage. This chapter discusses the earliest RBC parameter identified and is used for red cell disorders differentiation. Reticulocyte is a cell just one stage prior to the mature erythrocyte. There are various causes which lead to variation in the reticulocyte numbers having clinical significance. Red cell distribution width (RDW) is a quantitative measure or numerical expression of anisocytosis. In this chapter RDW is described in detail including its clinical application. RDW plays an important role in deciding the status of the red blood cells with reference to their production and damage. The chapter also highlights the importance of RDW in interpreting the types of anemia with respect to their etiology forming the basis for management.