The general field of rare diseases is particularly challenging because of the delays in reaching a diagnosis as well as the many trials and errors before effective treatment can be reached. To date there are approximately 7,000 rare diseases. Most of these are derived from a genetic basis thus affecting the individual from birth or early childhood. Furthermore, many of these diseases affect multiple systems creating devastating effects on patient and family alike. For example, many of these rare diseases impact the patient's motor, cognitive and respiratory skills. Frequently, patients are unable to swallow safely. This may lead to aspiration pneumonia and even death. The slow turn around rate in precisely identifying and treating these diseases can have a significant impact on mortality. This chapter presents a summary of a rare disease, Plummer-Vinson syndrome (PVS). One of the main characteristics of PVS is the significant dysphagia (swallowing disorder) that occurs due to the presence of esophageal webs. PVS is discussed in terms of its history, etiology, epidemiology, clinical presentation, diagnosis, treatment and the significant impact on swallowing that results.