There has been a major resurgence of tuberculosis (TB) and drug-resistant tuberculosis in the last few decades. Although it has been brought under control in most Western countries, it is still a major cause of death in endemic regions like India. Osteoarticular tuberculosis (OA TB) forms a small proportion of the total cases of tuberculosis. Perceptions and practices of orthopedic surgeons are entirely different in endemic and non-endemic regions around the world, due to the vast difference in exposure. Literature from endemic areas puts stress on clinico-radiological diagnosis and empirical anti-tubercular treatment (ATT). Such practices, although non-invasive, simple to implement, and economical, carry a significant risk of missing TB mimics and developing drug resistance. However, OA TB is still perceived as a “diagnostic enigma” in non-endemic regions, leading to a delay in diagnosis. Hence, a high index of suspicion, especially in a high-risk population, is needed to improve the diagnosis. Evolving drug resistance continues to thwart efforts to control the disease globally. This review article discusses the perceptions and practices in different parts of the world, with India as an example of the endemic world, and lays down priorities for overcoming the challenges of diagnosing osteoarticular TB.