Karl Landsteiner studied blood types in Europe and in the United States in the late nineteenth and early twentieth centuries. Landsteiner won the Nobel Prize in Physiology or Medicine in 1930 for detailing immunological reactions in the ABO blood group system. The ABO blood group system divides human blood into one of four types based on the antibodies that are present on each cell. Landsteiner's work with blood types led physicians to safely perform blood transfusions and organ transplants. Additionally, Landsteiner researched the Rh blood factor, a protein marker on the surface of blood cells and that can impact pregnancy.

The use of blood in forensic analysis is a method for identifying individuals suspected of committing some kinds of crimes. Paul Uhlenhuth and Karl Landsteiner, two scientists working separately in Germany in the early twentieth century, showed that there are differences in blood between individuals. Uhlenhuth developed a technique to identify the existence of antibodies, and Landsteiner and his students showed that humans had distinctly different blood types called A, B, AB, and O. Once doctors differentiated blood into distinct types, they could use that information to safely perform blood transfusions. Furthermore, forensic scientists could use that information to exculpate people suspected of some types of crimes, and they could use it to help determine the paternity of children.

William Thornton Mustard was a surgeon in Canada during the twentieth century who developed surgical techniques to treat children who had congenital heart defects. Mustard has two surgeries named after him, both of which he helped to develop. The first of these surgeries replaces damaged or paralyzed muscles in individuals who have polio, a virus that can cause paralysis. The other technique corrects a condition called the transposition of the great arteries (TGA) that is noticed at birth. Surgeons worldwide adopted that technique, leading to increased survival rates in infants afflicted with the condition. Mustard also published over 100 articles on congenital heart defects, surgical techniques, and the preparation of an artificial heart lung machine. Mustard helped perform the first blood transfusion of a newborn whose red blood cells (RBCs) had degraded, a condition called hemolytic anemia. Throughout his career, Mustard developed surgical techniques that increased the survival rates of infants and children with congenital and developmental disorders.

Radioimmunoassay (RIA) is a technique in which researchers use radioactive isotopes as traceable tags to quantify specific biochemical substances from blood samples. Rosalyn Yalow and Solomon Berson developed the method in the 1950s while working at the Bronx Veterans Administration (VA) Hospital in New York City, New York. RIA requires small samples of blood, yet it is extremely sensitive to minute quantities of biological molecules within the sample. The use of RIA improved the accuracy of many kinds of medical diagnoses, and it influenced hormone and immune research around the world. Before the RIA was developed, other methods that detected or measured small concentrations of biochemical substances required large samples of blood-- often too large for researchers to collect. With the development of RIA, researchers could use a single drop of blood to detect and measure the concentration of some biochemical substances. By 1970 doctors used RIA to measure follicle stimulating and luteinizing hormones to diagnose and treat infertility in women. Further developments led to neonatal screening programs for hypothyroidism.