In the last decades the severe issues related with fossil fuels depletion, increasing energy prices and global warming impact of energy conversion systems have attracted the efforts of scientists toward efficient technologies and methodological improvements for a rational use of energy both in the civil and the industry sectors. Among the numerous research lines developed, the combined production of multiple energy vectors and the process integration are widely considered very promising solutions to achieve more sustainable scenarios as concerns the use of energy. While polygeneration in industry represents a well-established practice to reduce the production cost of energy and material streams, the large potential existing for cogeneration and trigeneration in the building sector has been scarcely exploited for a number of reasons. The irregular electric, cooling and heating load profiles of a building (either in the residential or in the tertiary sector) throughout the year often make it difficult to operate a Combined Heat and Power (CHP) or a Combined Heat, Cooling and Power (CHCP) plant to operate effectively, with a full recovery of the heat cascades and reducing the energy costs. Also, a number of barriers as concerns the absence of a stable legislative framework and the scarcely harmonized suppor mechanisms for efficient polygeneration have further inhibited the marrket penetration of this technology. In the last few years our research group has developed a multi-targeted research activity, essentially oriented to: - Identify optimal design and operation criteria for cogeneration and trigeneration plants in buildings applications. Buildings in the tertiary sector, in particular, have represented main targets for these studies due to their higher potential for combined energy conversion systems; in particular, analyses have been performed for applications in hotels, hospitals, offices, university campuses and also in airports. Traditional methods for plant sizing based on the duration curve of heat loads have been modified into more refined techniques, based on the duration curve of the so-called “Aggregate Thermal Demand”. Also, as concerns the operation strategies for the CHP unit, the traditional approaches based on a “Heat Tracking” and an “Electricity Tracking” philosophy has been improved, identyfing hybrid and more convenient operation strategies oriented to either maximise the profitability, the energy saving or the pollutant emissions reduction [1]; - Analyze critically the legislative framework as concerns the “high efficiency CHP/CHCP” assessment developed after the “Directive 2004/8/EC on the promotion of cogeneration based on useful heat demand”. In particular, several critical aspects have been addressed on rigorous thermodynamic bases: the non discriminatory behaviour of the calculation methods for energy users characterized by peculiar load conditions [2], the most appropriate reference efficiencies for separate production used to evaluate the energy savings and, finally, the most efficient form of support mechanisms to promote a real spread of cogeneration and trigeneration systems in the civil sector. Also, promising scenarios as concerns flexible user-oriented criteria for the high efficiency CHP assessment have been developed; - Develop efficient algorithms for the simultaneous optimization of synthesis, design and operation for CHP and CHCP systems serving a single building or a cluster of buildings. The algorithms are based on Mixed Integer Linear Programming techniques, and they have been implemented in Matlab environment where efficient Lindo Api 8.0 solvers are run. When applied to a cluster of buildings (like a university campus or a polyclinic hospital), the optimization technique automatically indicates the optimal location of the units, the morphology of the district heating network to install and the hourly operation of each component, so as to minimize the payback time or maximise the profitability of the investment. Of course, support mechanisms like the attribution of white or green certificates or the eventual “emissions trading” are properly accounted for, thus leading to a sort of “multi-objective” optimization where energy savings and/or emissions reduction are included in the objective function. As concerns more complex polygeneration schemes, not specifically designed for buildings but rather for industrial applications, a peculiar use of heat cascades has been considered, that is related with feeding a thermal desalination unit like a Multiple Effect Desalination (MED) or a Multi-Stage Flash (MSF) plant. As such systems can be driven by a low grade heat source (like low pressure condensing steam or hot water at moderate temperatures, in the order of 75-85 °C), they could be considered suitable bottoming applications for cogeneration systems (i.e. topping power cycles) or, eventually, they may be integrated in large solar thermal polygeneration schemes. This kind of application is of particular interest in insulated communities (for instance, in small mediterranean islands) where fresh water scarcity often represents a severe issue. Energetic and exergetic analyses have been performed, thus mapping the efficiency of the main subsystems and auxiliaries and identifying the margins for improvements; also, approaches based on process integration have been considered by applying pinch analysis to some complex schemes. Finally, hybrid “Reverse Osmosis + MSF or MED” plants have been designed, based on the simultaneous use of a mechanically- and a thermally-driven desalination process and on blending the two desalted water flows which are tipically produced at very different salinities; such a hybrid configuration, when properly optimizes, allows to adjust the Power to Heat Ratio of energy inputs depending on the design of the coupled topping power cycle. Another innovative research line is related with improvements of design and maintenance of energy systems to be achieved through thermoeconomic analysis. For this methodology, whose main application field has been always identified in large scale power plants, two innovative possible uses have been identified, as follows: - Thermoeconomic cost accounting of polygeneration system operating in unsteady operating conditions: when properly designed for energy systems with variable operating conditions (for instance, cogeneration of heat by fossil fuel for buildings application or by solar sources), exergy costing allows to identify rational selling prices for each energy vector, which may be used when feed-in tariffs for surplus electricity are available or when surplus heat or cooling is sold to third parties connected to a district heating or cooling network; - Thermoeconomic diagnosis of refrigeration systems has been emerging as a promising approach to quantify, at any instant, the deviations from the nominal operating conditions provoked by different faults (condenser or evaporator fouling, compressor valve leakages, refrigerant leakage) occurring in a large-scale air conditioning unit. This aspect is extreemely relevant since air conditioning units are often poorly maintained and experience dramatic degradation of performance that induces much higher-than-nominal power consumptions.