Since the early days of HIV infection, back in the eighties, TB – particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an ‘AIDS defining condition’ according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection; and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood – or tissue – concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that – scant – resources had to be dedicated for the fight against the pandemic.