Wastewater treatment plants (WWTPs) are scrutinized by Environmental Authorities particularly regarding the compliance to discharge limit values fixed by national and local regulations. An integrated approach is necessary to achieve the objectives established with Directive 2000/60/EC (WFD) considering the ecological status of the receiving water body and the quality of the discharge. Specifically, documentary, technical, management and analytical controls should be developed. Moreover, integrative information on the behaviour of the activated sludge in the aeration tank can be useful for plant managers as well as for the regulating Authorities. The study presents the experience concerning WWTP regulation considering the analytic assessment of the discharge as well the monitoring of the Sludge Biotic Index (SBI) for activated sludge. Data from monitoring during the period 2008–14 on SBI values and chemical and microbiological data on the discharges of a sample of 35 WWTPs in the province of Venice (north-east Italy, Veneto region) are presented and discussed. Together with chemical and microbiological analysis, the SBI appears to be a highly useful index for the integrative assessment of plant functionality, in particular when monitoring and identifying critical situations that can determine the exceedance of discharge limit values. The SBI method, in an integrated control approach, can be used for small and medium sized WWTPs that only treat domestic wastewaters. In a case by case assessment this may even substitute part of the analytical monitoring carried out in the WWTPs' control process.