Ever since the first biologically active chemokines were discovered in the late 1980s, these messenger proteins and their receptors have been the target for a plethora of drug discovery efforts in the pharmaceutical industry, as well as in academia. Owing to the publication of several chemokine receptor X-ray crystal structures, a highly druggable, intracellular, allosteric binding site which partially overlaps with the G protein binding site was discovered. This intriguing, new approach for chemokine receptor antagonism has captured researchers around the world, pushing the exploration of this intracellular binding site and new antagonists thereof. In this review, we have highlighted the past two decades of research on small-molecule chemokine receptor antagonists that modulate receptor function at the intracellular binding site.