Mucins are large multifunctional glycoproteins whose primary functions are to protect and lubricate the surfaces of epithelial tissues lining ducts and lumens within the human body. Several lines of evidence also support the involvement of mucins in more complex biological processes such as epithelial cell renewal and differentiation, cell signaling, and cell adhesion. Recent studies have uncovered the role of select mucins in the pathogenesis of cancer, underscoring the importance of a detailed knowledge about mucin biology. Under normal physiological conditions, the production of mucins is optimally maintained by a host of elaborate and coordinated regulatory mechanisms, thereby affording a well-defined pattern of tissue-, time-, and developmental state-specific distribution. However, mucin homeostasis may be disrupted by the action of environmental and/or intrinsic factors that affect cellular integrity. This results in an altered cell behavior that often culminates into a variety of pathological conditions. Deregulated mucin production has indeed been associated with numerous types of cancers and inflammatory disorders. It is, therefore, crucial to comprehend the underlying basis of molecular mechanisms controlling mucin production in order to design and implement adequate therapeutic strategies for combating these diseases. Herein, we discuss some physiologically relevant regulatory aspects of mucin production, with a particular emphasis on aberrations that pertain to pathological situations. Our views of the achievements, the conceptual and technical limitations, as well as the future challenges associated with studies of mucin regulation are exposed.