•CHIKV is a re-emerging arbovirus that has caused major outbreaks in Africa, Asia and recently in the Americas.•The chronic phase of infection is characterized by painful polyarthralgia that may last for several months.•There are no approved vaccines or antivirals for prevention or treatment of CHIKV infection.•Several compounds that target a viral or a host factor inhibit the in vitro replication of CHIKV.•For most reported anti-CHIKV molecules, in vivo efficacy still needs to be evaluated in animal models. Chikungunya virus (CHIKV) has re-emerged in recent decades, causing major outbreaks of chikungunya fever in many parts of Africa and Asia, and since the end of 2013 also in Central and South America. Infections are usually associated with a low mortality rate, but can proceed into a painful chronic stage, during which patients may suffer from polyarthralgia and joint stiffness for weeks and even several years. There are no vaccines or antiviral drugs available for the prevention or treatment of CHIKV infections. Current therapy therefore consists solely of the administration of analgesics, antipyretics and anti-inflammatory agents to relieve symptoms. We here review molecules that have been reported to inhibit CHIKV replication, either as direct-acting antivirals, host-targeting drugs or those that act via a yet unknown mechanism. This article forms part of a symposium in Antiviral Research on “Chikungunya discovers the New World.”