This book chapter provides an overview of red blood cell (RBC) aggregation, covering its biophysical underpinnings, diverse measurement techniques, and clinical implications. Beginning with an introduction to the physical mechanisms of RBC aggregation, the chapter discusses several characterization techniques, such as Single-Cell Force Spectroscopy and Optical Tweezers, offering insights into the forces binding pairs of RBC together. Moving to bulk properties, the chapter emphasizes the significance of characterizing entire RBC populations for robust clinical comparisons. First, morphological analysis of RBC aggregates follows, introducing usual parameters extracted from image analysis. Afterward, the Erythrocyte Sedimentation Rate (ESR) takes center stage, exploring its historical roots, clinical practices, and physical mechanisms. A dual examination unveils the ESR’s role as both a diagnostic tool and a window into RBC physics. The physical mechanism section challenges historical views with the latest cutting-edge research, presenting a soft gel collapse model that considers the unique discocytic shape of RBCs. The chapter concludes by comparing ESR with optical properties, emphasizing the nuanced differences between syllectometry and ESR measurements. Encompassing biophysics, clinical correlations, and cutting-edge techniques, this chapter offers a holistic understanding of RBC aggregation, providing a valuable introductive resource for researchers, clinicians, and students in the field.