The biophysical characteristics and counts of blood cells provide useful information regarding pathological conditions. Therefore, the separation of blood components is a crucial task in biology, clinical diagnosis, therapeutics, and personalized medicine. Recently, microfluidics has gained significant interest as an effective technology for separating target cells from heterogeneous cell populations. Within cellular-scale microchannels, cells of interest are separated based on intrinsic properties, such as size, shape, and deformability, followed by further downstream or off-chip analysis. In this review, microfluidic-based hydrodynamic cell-separation technologies used in label-free approaches by categorizing them according to their key working principles are discussed: i) flow fractionation, ii) deterministic lateral displacement, iii) hydrophoresis, iv) inertial migration, and v) microfiltration. An overview of the major separation mechanisms is provided, and the relative performances and features of these technologies are thoroughly discussed. In addition, future perspectives regarding microfluidic system commercialization and standardization are briefly provided for their widespread use and applications.