Dendritic cells (DCs) are professional antigen presenting cells responsible for immune homeostasis. In the lung's responses to tissue damage or infection they initiate and orchestrate innate and adaptive immunity. There are immature and mature states and at least 3 phenotypic and functional subsets. DCs circulate in the blood and localise to mucosal surfaces in immature form where they act as sentinels, sampling constituents of the external environment that breach the epithelium. With internalisation of antigen they are activated, they mature and migrate to draining lymph nodes to induce the proliferation and regulate the balance of Th1/Th2 T-cells or to induce a state of tolerance, the last dependent on maturation status, extent of cell surface co-stimulatory molecule expression and cytokine release. Cigarette smoke has modulatory effects varying with species, dose, the location examined within the lung and the marker or technique used to identify DCs. Healthy smokers (and asthmatic smokers) have reduced numbers of large airway mature DCs. In chronic obstructive pulmonary disease (COPD) the number of immature DCs is increased in small airways whereas, in smokers with COPD, the total number of DCs appears to be reduced in large airways. We hypothesize that the long-term effects of cigarette smoke include reduction of DC maturation and function, changes that favor repeated infection, increased exacerbation frequency and the altered (CD8⁺ T-cell predominant) pattern of inflammation associated with this progressive chronic disease.