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To know the composition of blood and the benefits rendered by its components to life has been a question that for centuries stimulated the curiosity of researchers. Each of the human knowledge eras has provided its own explanation and gradually contributed with a series of discoveries, which by accumulating, have allowed to explain the physiological processes of this fluid, considered like vital since the most remote times. From being one more of the four humors that constitute living matter, according to ancient medicine, blood became, during seventeenth century, a mixture of fluids and diverse particles moved incessantly by the action of the heart. Once the iatromechanical aspect of blood circulation was known, the researchers approached the problem of its composition, using the new scientific tools (observation, experimentation and measurement), such as the microscope, quantification instruments, stains and chemical reagents, that appeared during the Baroque Period and later. During seventeenth century erythocytes were discovered as well as the metallic nature of blood when iron particles were detected in it. In the eighteenth century, leukocytes were discovered and, almost a century later, platelets were added. One of the great mysteries to solve, the coagulation of the blood, began to be deciphered in the seventeenth century, when fibrin was observed in the structure of the clots. Thrombin and tissue factor was discovered during nineteenth century. At the beginnings of the twentieth century, the morphology and origin of blood cells became known, as well as their variations during some diseases. The bases for the clinical laboratory, the hematology clinic and some therapeutic procedures, such as blood transfusion, developed. Separation of plasma components, cellular identification techniques, inheritance laws, and the talent to construct instruments for ever increasing precise analyses gave rise to the numerous specialties in science that has studied the blood: Hematology, Immunology, Clinical Biochemistry, Clinical Pathology, Hemostasis and Thrombosis, Transfusional Medicine, Hematogenetics, Chemotherapy and many others.