India has a long and distinguished tradition of research in the field of tuberculosis (TB). Pioneering studies from India demonstrated the efficacy and safety of domiciliary treatment, the necessity of direct observation of treatment, the feasibility of case detection through sputum smear microscopy in primary health care institutions, and the effectiveness of intermittent short-course chemotherapy. These findings laid the foundation of directly observed treatment, short course (DOTS), which has been adopted by nearly 150 countries worldwide. Today, India has the second-largest and the fastest-growing DOTS programme in the world. A strong component of programme evaluation and operational research is needed to sustain and expand DOTS in the context of a suboptimal primary health care system, a large and unregulated private health care system, and the dual threats of HIV and multidrug-resistant TB (MDR-TB). Therefore, the focus of TB research in India has shifted to the following operational research areas: evaluating models to involve the private health sector; assessing the role of incentives in increasing treatment compliance; examining gender differentials in the access to TB services; assessing risk factors for delay in diagnosis; evaluating diagnosis, treatment and prevention of TB among HIV-infected persons; monitoring MDR-TB; estimating cost-effectiveness of the DOTS programme; monitoring the quality of smear microscopy services; and measuring the current burden of TB. Research for developing newer diagnostic tools, drugs and vaccines remains a long-term priority. Greater networking is needed among national researchers, programme managers and policy-makers to translate the findings of research into policies and programmes to make TB control in India more effective and efficient.