Vitamin D has been increasingly recognized as being involved in a wide spectrum of biological actions, including significant immunomodulatory effects. The cystic fibrosis (CF) airways are characterized by dysregulated and disproportionately increased, in relation to the underlying bacterial stimuli, inflammatory responses. Vitamin D downregulates pro-inflammatory cytokines and chemokines that promote tissue destruction, and which are abundant in CF lungs. However, despite mounting evidence for a pathophysiological role of Vitamin D in CF airways inflammation, there are only a few clinical reports supporting a relevance of Vitamin D insufficiency with CF airways damage, and so it is early to assign an indisputable causal role to Vitamin D. The present review will examine the current literature regarding the association of Vitamin D status with CF lung disease, and comment on the therapeutic implications accruing from these relations.