The aim of this thesis is to evaluate and optimise current pharmacotherapeutic options in rhinosinusitis. There is often a marked variation in treatment response in those afflicted with chronic rhinosinusitis, both within and between patients, attributable in part to different disease phenotypes/endotypes, poor awareness of treatment optimization options, and trivialization of symptoms by patients and physicians. Characteristically, these factors contribute to a typical remitting and relapsing disease course. The objectives of this work are to improve the therapeutic index and reach of commonly used medications by boosting efficacy whilst reducing concomitant side effects. The third chapter explores the use of initial oral steroids in patients with chronic rhinosinusitis and nasal polyposis, focusing on the role of the ostiomeatal complex in the perpetuation of disease symptoms. Often a short course of oral steroids is used in patients with moderate to severe disease to achieve initial control before maintenance with intranasal steroids. This is termed as a ‘medical polypectomy’ and anecdotally is commonly used in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the evidence for its efficacy is tenuous and there are no data to evaluate if it indeed re-establishes ostiomeatal sinus complex drainage which is a condicio sine qua non of ensuring long-term symptom resolution. Further, it is known that monotherapy with nasal steroids may result in loss of symptom control. We have therefore in a double-blind placebo controlled trial (Chapter 4) evaluated the effect of this initial induction with oral steroids on subsequent sequential intranasal therapy. Perhaps, however, more crucially we have for the first time comprehensively addressed the safety of both oral and topical steroids in patients with CRSwNP who have other concomitant steroid-dependent illnesses like asthma and COPD. A particularly refractory subset of those with CRSwNP also have aspirin intolerance and asthma. While recent guidelines have recommended more aspirin challenge testing in these patients, it is unclear what the significance of a positive test is in the absence of overt clinical symptoms or in patients with only moderate disease. This is addressed in Chapter 5, as this significant phenotype of aspirin intolerant rhinosinusitis need close monitoring, dose optimization, polytherapy, and in selected cases may be suitable for aspirin desensitization. Penultimately, we evaluate in a double-blind placebo controlled trial (Chapter 6) the tachyphylaxis and rebound congestion that blights the medium to long-term use of sympathomimetic nasal decongestant sprays like oxymetazoline and if this can be reversed by the concomitant use of nasal steroids. We also characterized nasal blood flow as an outcome to evaluate in these patients and its relation to other rhinological outcome measures (Chapter 7).