This chapter considers the respiratory delivery of drugs used in the treatment of tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis. It provides a rationale for respiratory delivery of anti-tubercular drugs to the lungs, including the targeting of alveolar macrophages and granulomas. The doses of anti-tubercular drugs are high and most formulations will be carrier free containing drug and limited amounts of excipient. The aerosolization of high dose drugs existing in a cohesive matrix will be related to de-agglomeration processes. The chapter outlines the studies that have occurred in this area using particle engineering approaches. Formulations of particles or engineered particles which possess a suitable size for respiratory delivery can be considered as cohesive matrices. The particles in the matrix will interact due to the various interactive forces that exist between particles, including contact potential forces, Coulombic forces, intermolecular forces, capillary force and solid bridging.