The complete blood count (CBC) has by and large remained confined to the traditional laboratory setting since its inception. Used in a variety of diagnostic assessments, the CBC has essentially become limited to clinical laboratories because of reliance on large automated hematology devices. With many potential uses at the point of care and clinical settings, as well as the research laboratory, a portable low-cost hematology analyzer could aid in earlier detection of a wide variety of medical conditions. Using smaller sample volumes, inexpensive polymers, and low power consumption, microfluidic devices present one such route toward miniaturization of the traditional flow cytometer-based hematology analyzers. This review focuses on challenges for development of cost-effective portable analyzers, potential areas for point-of-care clinical usage, current commercial systems with increasing portability, and recent research in improved miniaturization and automation, including developments in acoustic and inertial focusing techniques and novel detection methodologies. (JALA 2010; 15:319-28)