The incidence of infectious diseases has risen sharply in recent decades. The factors cited are generally those associated with ongoing global changes, including climate change, the loss of biodiversity, and increased international trade. In this study, we analyze the factors that may explain epidemics (as defined by the WHO) of human infectious diseases at the European level. To this end, we have compiled a database containing socioeconomic, environmental, and biodiversity variables for each country, as well as the major human infectious diseases reported there. Over the period from 1950 to 2010, there were 114 epidemic infectious diseases spread across 36 countries. These data confirm the nearly exponential increase in the number of epidemic infectious diseases over the past few decades. The total number of diseases recorded in European countries appears to be correlated with the country’s geographic area and its biodiversity (richness in bird and mammal species). This holds true for the total number of epidemic diseases, which also depends on the country’s population size, temperature variability, and economic wealth (GDP). The effect of the North Atlantic Oscillation (NAO) as an index of climate variability in Europe is tested for 13 analyzable infectious diseases over the past sixty years. Eleven infectious diseases show occurrences associated with monthly variations in the NAO index, such as hantavirus hemorrhagic fevers, tularemia, Q fevers, trichinosis, and bacterial or viral gastrointestinal infectious diseases. This study highlights the potential value of monitoring changes in biodiversity or climate variability for early warning systems in epidemiological surveillance. (R.A.)