The nasal cavity is both a target for locally and systemically acting medications. An adequate treatment for rhinosinusitis continues to be an unmet need. With the recent approval of intranasal medications for the treatment of pain, the nasal cavity continues to be a viable route for rapid uptake into the systemic circulation. Despite the opportunities, there is still a void in the knowledge of how therapeutic entities interact with the nasal epithelium. In addition, new opportunities in mucosal immunity via nasal vaccination as well as the elusive nose to brain uptake continue to drive innovation. To facilitate understanding of the issues involved that facilitate drug delivery in the nose, a review of nasal morphology and physiology is presented.