As other cytokine families, chemokines have multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage. Chemokines play important roles in leukocyte trafficking and leukocyte activation, hence, blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicate that additional roles of chemokines in the regulation of innate and adaptive immune responses may adversely affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential and possible adverse effects of anti-chemokine strategies in renal inflammation.