Alterations to bronchi and bronchioli during the distinct phases of human intrauterine development, at birth, or in infancy may predispose people to the later development of airflow limitation. Both genetic and exogenous factors, such as fetal or neonatal passive exposure to tobacco smoke, viral lower respiratory tract infection, prematurity, or neonatal mechanical ventilation, may influence development. This synopsis considers the key differences between large and small airways of the human lung and their development. A more detailed consideration of the structural and biochemical changes associated with lung development is provided elsewhere (1–4). The end point for airway and lung development is a gas-exchanging organ in which air and blood come into intimate contact over a large surface area that maintains communication with the exterior. An oxygen uptake of up to 3 L/min is facilitated by an air-blood contact area approximately half the size of a singles tennis court (approximately 80 m2). The barrier separating air and blood is only 0.2 m thick—1/50 the thickness of a sheet of airmail paper. The respiratory region’s communication with the exterior is afforded by a system of asymmetric, dichotomously branching tubes that extend peripherally to the visceral pleura from the larynx and trachea. Airways are usually designated by structure and order of division: those distal to the trachea with cartilage in their walls are bronchi. In the trachea, supportive cartilage is present in the form of irregular, sometimes branching, rings (16–20 in humans), all of which are incomplete dorsally, where they are bridged by connective tissue and bands of smooth muscle. In large bronchi the cartilages are irregular in shape but frequent enough to be found in any plane. In small bronchi, they are less frequent and may be missed in transverse section. Airways distal to the last cartilage plate are termed bronchioli. The last bronchiolar divisions have their ciliated epithelium lining interrupted by alveoli and are referred to as respiratory bronchioli; the generation proximal to the first-order respiratory bronchioles are referred to as terminal bronchioli. Terminal bronchioli form the last purely conductive airways, and the respiratory bronchiolus is the site where gaseous exchange begins. There are generally three orders of respiratory bronchioli. A single terminal bronchiolus with its succeeding respiratory bronchioli and two to nine orders of alveolar ducts and alveolar sacs together form the respiratory acinus, which is about 1 cm in diameter and forms the basic respiratory unit of the lung. Detailed differences between large and small airways have been published previously (5–7). In general, airway epithelium becomes thinner more peripherally, and cilia become shorter and more sparse than in large airways. Bronchial epithelium contains about 6,000 mucus-secreting goblet cells (Figure 1) per mm2 of surface. These goblet cells and basal cells are rarely found in bronchioli (5, 6), where nonciliated Clara cells (Figure 2) are the main secretory and stem cell. In contrast, basal and goblet cells form the stem cell of the large airway. Submucosal glands are present wherever there is cartilage.