In the Salento peninsula (Puglia Region, South-East Italy), underground waters are a fundamental resource for the population because they constitute the principal reservoir for drinking water and irrigation. They are, however, affected by overexploitation. The risk factors in the Salento arise mainly from anthropic activities, especially tourism and agriculture (leaking wells, sewage and inadequate waste disposal procedures). The Southern Salento is recognized to be at high risk of pathologies characterised by oral-faecal transmission. From 2001 to 2009 the incidence of typhoid fever in the Salento was 12.11/100,000 inhabitants as against 2.91 in Italy. Enteritis caused by rotaviruses is an important cause of hospitalization of paediatric-aged children in the Salento, with high social costs. An effective monitoring system for the conservation and management of water bodies and the protection of public health is therefore fundamental. The present study sought to determine the microbiological and chemical-physical quality of groundwater in the Salento and to analyse the factors associated with contamination. The results indicated widespread pollution from salt and microbial contamination. Contamination from faecal microorganisms posed a significant risk of human infection in 100% of samples. Furthermore, the water was unsuitable even for irrigation in a high percentage of cases (31.8%), which is of considerable significance given that agriculture is one of the most important economic activities in the area under study. The high salt concentration was probably due to excessive extraction of water for intensive irrigation, especially in summer. Under these circumstances, some of mitigation activity is necessary. Furthermore, it would be advisable to decrease the pollution load from anthropic activities in the territory and to reduce water consumption in order to conserve groundwater resources especially.