Since the identification of the chemokine receptors CXCR4 and CCR5 as co-receptors for HIV-1 entry, several antagonists against these receptors have been synthesised. A highly selective CXCR4 antagonist, T22, and its downsized analogues T140 and TC14012, which inhibit X4-HIV-1 infection through their specific binding to CXCR4, have been identified. Besides T22 analogues, several other CXCR4 antagonists have been reported, such as AMD3100, ALX40-4C, KRH-1120 and AMD8664. Discovery of entry inhibitors, such as chemokine antagonists, may lead to the development of a new generation of antiHIV agents, since these inhibitors are thought to be useful for the clinical treatment of HIV-1-infected patients, especially at the late stage of treatment for AIDS patients developing multi-drug-resistant strains. In this review, recent research into CXCR4 antagonists in comparison with development of other antagonists is summarised.