HIV-1 integrase (IN), which has no cellular counterpart, has been intensely studied over the past 15 years and has been fully validated as a therapeutic target with the first FDA approved IN inhibitor raltegravir. The quinolone acid GS-9137 (elvitegravir), which most probably will became the next candidate of IN inhibitors, is in the process of enrolling patients in the phase III clinical trials. This review focuses on small-molecules of quinolone acid derivatives, which have the similar pharmacophore of β-diketoacids, as integrase inhibitors with antiviral activity.