Hemozoin, a bio-crystalline substance, is a hemin detoxification by-product of malaria parasites. The role of hemozoin crystals in host immune system modulation by malaria parasites, and how they interact with the immune system has been enigmatic. Here, we summarize recent progress in our understanding of how hemozoin might be interacting with the host immune system. In particular, the potential application of hemozoin crystals as an adjuvant may provide insights into the molecular mechanisms involved in immune responses to malarial infection and provide a rationale for the design of vaccines against malaria as well as other immunological disorders such as allergies.