Fluoroquinolones (FQ) play an essential role in the treatment and control of multidrug-resistant tuberculosis (MDR-TB). They are also being evaluated as part of newer regimens under development for drug-sensitive TB. As newer FQ-based regimens are explored, knowledge of FQ resistance data from high TB burden countries becomes essential. We examine available FQ resistance data from high TB burden countries and demonstrate the need for comprehensive surveys to evaluate FQ resistance in these countries. The factors driving FQ resistance in such conditions and the cost of such resistance to weak healthcare systems are discussed. The need for a comprehensive policy for addressing the issue of FQ resistance is highlighted.