The variability of the insect-borne disease dengue in Puerto Rico was studied in relation to climatic variables in the period 1979–2005. Annual and monthly reported dengue cases were compared with precipitation and temperature data. Results show that the incidence of dengue in Puerto Rico was relatively constant over time despite global warming, possibly due to the offsetting effects of declining rainfall, improving health care and little change in population. Seasonal fluctuations of dengue were driven by rainfall increases from May to November. Year-to-year variability in dengue cases was positively related to temperature, but only weakly associated with local rainfall and an index of El Nin˜ o Southern Oscillation (ENSO). Climatic conditions were mapped with respect to dengue cases and patterns in high and low years were compared. During epidemics, a low pressure system east of Florida draws warm humid air over the northwestern Caribbean. Long-term trends in past observed and future projected rainfall and temperatures were studied. Rainfall has declined slowly, but temperatures in the Caribbean are rising with the influence of global warming. Thus, dengue may increase in the future, and it will be necessary to anticipate dengue epidemics using climate forecasts, to reduce adverse health impacts.