SENTIERI Project is the first comprehensive study of the health impact of residence in Italian polluted sites (IPSs). The present Chapter examines the main validity aspects of the present mortality investigation and the evaluation of causality of the observed associations; in addition, some recommendations for public health intervention and research priorities in epidemiological studies on environment and health are given. Exposure ascertainment is a key aspect when an ecological study design is adopted in environmental epidemiology, therefore any exposure potentially affecting the population at study should be described in detail. This is here discussed. SENTIERI is an ecological study, based on a priori hypotheses, in which each IPS's types of exposure were described with specific attention to human exposure. Though, when commenting the results, the problem of concurrent air pollution exposure and/or industrial activities implying occupational risk, if present in the IPSs, was taken into account. Socioeconomic status is a determinant of health and disease, therefore in SENTIERI the Standardized Mortality Ratios were computed both crude and adjusted for an ad hoc deprivation index. About 60% versus an expected 40% of IPSs residents are in the two most deprived quintiles of the index. This hints to a possible problem of environmental justice that should be taken into account when planning remediation intervention. The mortality results here presented are a first step in the epidemiological IPSs' characterization, and some developments have been made or planned. Firstly, a mortality analysis was performed combining mortality data in IPSs presenting similar pollution, i.e. asbestos, or industrial hazardous wastes or dumping sites; secondly, the mortality analysis will be extended beyond 2002, namely the year when ICD X started to be in use in Italy. In addition, disease prevalence will be investigated using hospital discharge records; cancer incidence and congenital anomalies incidence will be studied in IPSs in which a Cancer Register or a Congenital Anomalies Register are active. The above described activities will lead to a more valid estimate of the disease burden of IPSs residents, and allow to identify priorities of remediation activities. The method adopted in SENTIERI, specifically the ecological design and the use of mortality data at municipal level, in general does not grant the evaluation of the causal association between environmental exposure and adverse health effects. However, it allows etiological observations that make unacceptable the delay of remediation intervention.