The role of fluoroquinolones (FQs) in the management of drug-susceptible and drug-resistant tuberculosis (TB) is under investigation. They are currently being used off-licence to treat TB patients who develop hepatotoxicity on standard therapy, and in patients with drug-resistant disease. Prolongation of ventricular repolarisation, recorded as lengthening of the QT interval on an electrocardiogram, is a recognised adverse effect associated with FQs. Significant prolongation of the QT interval may precipitate torsades de pointe, a potentially fatal tachyarrhythmia. Currently licensed FQs are considered safe, and there are very few reports of associated arrhythmias, but most labels contraindicate concomitant administration of other agents that prolong QT. In many high TB burden countries, malaria is also endemic. Many antimalarials, and possibly malaria infection itself, may prolong QT; under current licence, co-administration of FQs with these antimalarials is contraindicated due to potential risk of additive QT prolongation. This poses significant challenges in planning future policy on FQ use for first-line anti-tuberculosis treatment; the duration of TB treatment makes concomitant malaria treatment inevitable, and options without FQ contraindications are limited. Furthermore, malaria diagnosis is often poor and access to treatment uncontrolled, with many patients buying 'over-the-counter' and/or 'traditional' remedies; concomitant use with anti-tuberculosis treatment is thus likely to be unregulated. Drug interaction studies are urgently required to assess the safety of managing patients with TB and malaria within endemic, resource-poor settings where programmatic management and low-cost monitoring are essential for effective implementation of public health strategies.