This chapter deals with the discussion on pathogenesis of tuberculosis (TB). A person with active but untreated TB may infect at least 10–15 other people per year. Transmission only occurs from people with active TB and not with latent infection. Probability of transmission depends upon several factors: number of infectious droplets expelled by the carrier, effectiveness of ventilation, duration of exposure, virulence of the Mycobacterium tuberculosis strain, and level of immunity in the uninfected person. In immunosuppressed states like human immunodeficiency virus (HIV) infection, immunosuppressant drug use (steroids, cyclophosphamide, cancer chemotherapy etc.), certain occupations, certain malignant diseases, and organ dysfunction states, the chances of developing the disease increases. By and large it is a self-limiting infection without progression to disease in a majority of cases. Certain other factors also increase the risk of tuberculosis. Almost any organ of the body can be affected by tuberculosis. The infection can also remain dormant for a long period of time and with certain conditions can be reactivated. Interferon-γ plays an important role in protection. In the process, the effects of proinflammatory (TNF) and anti-inflammatory (IL-10) cytokines play important roles on the spectrum of phagocyte populations (macrophages and dendritic cells) in the lung and lymph node.