The CBC count and leukocyte differential count (LDC) are among the most frequently requested clinical laboratory tests. These analyses are highly automated, and the correct interpretation of results requires extensive knowledge of the analytic performance of the instruments and the clinical significance of the results they provide. In this review, we analyze the state of the art regarding traditional and new parameters with emphasis on clinical applications and analytic quality. The problems of some traditional parameters of the CBC count, such as platelet counts, some components of the LDC such as monocyte and basophil counts, and other commonly used indices such as red cell volume distribution width and platelet indices such as mean platelet volume and platelet distribution width are considered. The new parameters, evaluated from analytic and clinical viewpoints, are the available components of the extended differential count (hematopoietic progenitor cells, immature granulocytes, and erythroblasts), the immature reticulocyte fraction, the reticulocyte indices, the fragmented RBCs, and the immature platelet fraction.