Host-directed immunotherapy (HDI) is emerging as a transformative strategy in managing chronic diseases by leveraging the host's immune system to combat disease. This innovative approach has shown promise in a range of conditions, including cancer and parasitic infections. In oncology, HDI aims to enhance the body's natural immune response against cancer cells through mechanisms such as immune checkpoint inhibition, monoclonal antibodies, and cytokine therapies. These strategies are designed to boost the immune system's ability to recognize and destroy tumors, improving patient outcomes and offering alternatives to traditional cancer treatments. Similarly, in parasitic infections, HDI focuses on strengthening the host's immune defenses to control and eradicate those infections. For diseases like malaria, leishmaniasis, and Chagas disease, HDI strategies may involve adjuvants or immune modulators that amplify the body's ability to target and eliminate parasites. By optimizing immune responses and reducing reliance on conventional treatments, HDI holds the potential to revolutionize therapeutic approaches across various chronic diseases. This chapter highlights the flexibility and potential of HDI in advancing treatments, offering novel ways for improving patient care and disease management.