Platelet count and morphology are essential parameters in the routine diagnostic work-up and follow up of patients with various disorders. Their assessment is primarily conducted using automatic cell counters that rely on different principles and are increasingly available in the majority of clinical laboratories. In contrast, manual (microscopic) methods play a limited role, primarily reserved for complex diagnostic cases. Despite significant technical improvements in recent decades, challenges persist, including the potential for falsely elevated or reduced platelet counts, as well as inaccuracies in the determination of platelet size, which can complicate the diagnostic work-up. In addition, recent advances in understanding the factors that contribute to interindividual variability in platelet count and size have led to a reassessment of their reference intervals, raising concerns about their universal applicability. In this chapter, we will review the principal methodologies currently used to assess platelet count and size. Furthermore, we will go through the medical conditions associated with changes in platelet count and/or size, aiming to facilitate the differential diagnosis.