Chronic rhinosinusitis (CRS) is a heterogenous disorder and represents a major public health problem. Although insights into the pathophysiology of CRS have largely expanded over the last two decades, the exact etiology and mechanism of persistence is still unrevealed. CRS is a multifactorial disease, and, with variable evidence, impaired ostial patency, mucociliary impairment, allergy, bacterial or fungal infection (or triggering), immunocompromised state, and environmental and genetic factors have been suggested to be associated or risk factors. Pathomechanisms in CRS are better understood currently, allowing us to characterize and differentiate the heterogeneous pathology of chronic sinonasal inflammation based on histopathology, inflammatory pattern, cytokine profile, and remodeling processes. In nasal polyposis (NP), but not CRS without NP, an abundant eosinophilic inflammation and local immunoglobulin E production could be demonstrated, and Staphylococcus-derived superantigens may at least modulate disease severity and expression. These findings question the current assumption that NP is a subgroup of CRS, but suggest that CRS and NP should probably be considered as distinct disease entities.