Tuberculosis (TB) is a global epidemic of considerable proportions. It is also closely entwined with the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). There is a great need for new drugs, vaccines, and diagnostics in this therapeutic area, but there are many challenges in the successful operational execution of the requisite clinical trials in developing countries. This paper reviews these challenges and offers some ‘lessons learned’ in the execution of clinical trials for TB vaccines, treatment, and diagnostics across Africa, Asia-Pacific, Latin America, and eastern Europe over the past 10 years. To set the scene for these discussions, the paper first provides some background on the disease itself, existing vaccines and drugs, and current research on new products. Extensive references are provided for readers who wish to pursue these topics in greater detail.