The spectrum of pulmonary pathology in the Middle East is as versatile as its civilizations and cultures. In this review, we outline the key challenges confronting pulmonologists in the Middle East. We shed light on the diverse conditions commonly encountered in the region, from the centuries-old illnesses of tuberculosis, to contemporary problems such as lung complications from chemical warfare. We specifically highlighted unique aspects related to respiratory illnesses in the Middle East, for example, climate factors in the desert region, cultural habits, for example, water-pipe smoking and disorders unique to the region, such as Behçet's disease. Pulmonologists are also faced with the consequences of modernization, including large immigrant population and associated social and health issues, rising incidence of obesity and sleep apnoea, and drug-resistant tuberculosis. Tackling these health issues will require an integrated approach involving public health, primary care as well as specialist pulmonology input, taking into consideration the unique cultural and environmental factors to ensure effective management and compliance to medical care.