Mucus production is a primary defense mechanism for maintaining lung health. However, the overproduction of mucin (the chief glycoprotein component of mucus) is a common pathological feature in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and lung cancer. Although it is associated with disease progression, effective therapies that directly target mucin overproduction and hypersecretion are lacking. Recent advances in our understanding of the control of mucin gene expression in the lungs, the cells that produce airway mucins, and the mechanisms used for releasing them into the airways have provided new potentials for the development of efficacious interventions that will be discussed in this review.