The contribution of twin studies towards unraveling the complex mechanisms of multifactorial diseases is increasingly recognized. Recent twin studies using infant vaccination as a model for infectious diseases have confirmed the importance of host genetic factors as major regulators of the immune response. A combination of twin-based family studies and population-based association studies should lead to the identification of the specific genes involved. These genes and their products have the potential to be developed as targets for novel therapeutic and prophylactic agents against infectious diseases.