The re-emergence of Chikungunya fever, an old tropical infectious disease with new characteristics represents a major public health problem with severe social and economic burdens globally. Though Chikungunya has previously been known as a relatively benign disease, its recent re-emergence has caused considerable morbidity with even some cases of fatality. The aggressive waves of the disease are suspected to be due to changes in the virus as well as the vector which makes it appear like a new form of the disease. The study of the human immune response will be crucial in understanding some features of the disease. This review discusses what is currently known on the immuno-biology of Chikungunya and areas that will be important for the development of immune-based antiviral control strategies.