Despite a steady global decline in the incidence of tuberculosis (TB), progress towards health targets has been slow and a crisis of drug-resistant strains of TB continues unabated. The United Nations high-level meeting on TB in September 2018 resulted in a renewed push to invest in drugs, diagnostics and vaccines to “reach” those most vulnerable to the disease. Yet, an overriding focus on biomedical technologies to manage TB at the expense of meaningful engagement with the social threatens to further consolidate its reputation as a “silent killer.” Drawing on anthropological contributions from South Africa and one from neighbouring Zimbabwe, this special issue explores how human action produces, shapes, names, experiences and resists the disease in its fullest breadth within local conditions. The articles recognise TB as a “global” object of biomedical knowledge and intervention, on the one hand, and as intricately tied to a legacy of colonial and apartheid governance, on the other. Each article deals with different aspects of understanding the interface between global and national policies and their unintended effects in local worlds.