Chemokines belong to the group of small proteins within the cytokine family having strong chemo-attractant properties. In most cases, the strong immuno-modulatory role of chemokines is crucial for generating the immune response against pathogens in various protozoan diseases. In this review, we have given a brief update on the classification, characterization, homeostasis, transcellular migration, and immuno-modulatory role of chemokines. Here we will evaluate the potential role of chemokines and their regulation in various protozoan diseases. There is a significant direct relationship between parasitic infection and the recruitment of effector cells of the immune response. Chemokines play an indispensable role in mediating several defense mechanisms against infection, such as leukocyte recruitment and the generation of innate and cell-mediated immunity that aids in controlling/eliminating the pathogen. This process is controlled by the chemotactic movement of chemokines induced as a primary host immune response. We have also addressed that chemokine expressions during infection are time-dependent and orchestrated in a systematic pattern that ultimately assists in generating a protective immune response. Taken together, this review provides a systematic understanding of the complexity of chemokines profiles during protozoan disease conditions and the rationale of targeting chemokines for the development of therapeutic strategies.