Hemolytic disease of the newborn (HDN) is a potentially fatal condition caused by a Rhesus (Rh) antigen incompatibility between a mother and fetus. As a result, determining the Rh status of expectant parents is a routine clinical assessment. Both the physiological and immunological basis of this condition are taught to undergraduate students. At the University of South Australia, some undergraduate immunology students find this topic challenging. The author designed, implemented, and assessed the impact of an interactive simulation to facilitate student learning of HDN. The students were actively engaged in determining the blood grouping and Rh status of an expectant mother and father and then determining the possibility of developing HDN. The simulation was found to take only 15 min to complete yet led to a significant increase in student performance in an end of semester exam question. Student perceived understanding was found to significantly improve following the introduction of the simulation, even though the content had been covered in a formal lecture. Student feedback was highly positive of this learning approach. In conclusion, short, interactive simulations can be used effectively to enhance student learning of challenging concepts.