Paleopathology contributes to the knowledge of health and disease in past populations. In the case of tuberculosis, paleopathological research contributes to a better understanding of the antiquity and spread of the disease around the globe, as well as in Portugal. These aspects are the objectives of this work. Genomic research on the Koch bacillus indicates a co-evolution with African Homo sapiens. However, macroscopic, microscopic, imaging and biomolecular analyzes of human skeletal remains suggest that tuberculosis (TB) began to affect humans during the Neolithic period. For several decades the paleopathological diagnosis of tuberculosis was essentially based on the identification of Pott’s disease. More recently, the study of identified skeletal collections has revealed a statistically significant association between both new bone formation on the visceral surface of the ribs and hypertrophic osteoarthropathy and cause of death by pulmonary tuberculosis. Therefore, these skeletal signs have been used to assist in the differential diagnosis of pulmonary TB. Portugal, as in many other countries, notably European countries, was greatly affected by tuberculosis. However, the paleopathological record in the national territory can be considered quite scarce. Amongst the 8000 individuals studied from archaeological excavations, only 81 have bone changes compatible with the disease. Continued research on human and animal osteological remains will certainly bring new developments concerning the antiquity, evolution and spread of tuberculosis across populations and continents.