The mounting evidence for anthropogenic changes in global climate raises many pressing questions about the potential effects on biological systems, and in particular the transmission of infectious diseases. Vector-borne diseases, such as dengue, may be particularly sensitive to both periodic fluctuations and sustained changes in global and local climates, because vector biology and viral replication are temperature- and moisture-dependent. This paper reviews the current state of knowledge on the associations between climate variability, climate change and dengue transmission, and the tools being used to quantify these associations. The underlying causes of dengue’s recent global expansion are multifactorial and poorly understood, but climatic factors should be considered within the context of the sociodemographic, economic and immunological determinants that have contributed to dengue’s spread. These factors may mediate the direct effects of climate on dengue and many may operate at a very local level. Translating theoretical models of dengue transmission based on historical data into predictive models that can inform public health interventions is a critical next step and efforts should be focused on developing and refining models at smaller spatial scales to characterize the relationships between both climatic and non-climatic factors and dengue risk.