The conversion of sunlight into electricity represents a solution to the energy crisis. The cost of this kind of energy is still higher than that obtained from conventional sources limiting large scale applications. A promising approach to decrease the cost of photovoltaic devices, mainly made with inorganic materials, is the fabrication of solar cells based on organic semiconductors, like semiconducting polymers. Actually, power conversion efficiencies surpassing 5% have been demonstrated for polymer-fullerene solar cells, but to use these devices in commercial applications this value need to be increased further; in addition other aspects, like the large area processing and the lifetime also need to be improved. The power conversion efficiency for a solar cell is directly proportional to the short circuit current (Isc) and to the open circuit voltage (Voc). The maximum Voc for polymer solar cells is related to the difference between the highest occupied molecular orbital (HOMO) of the electron donor and the lowest unoccupied molecular orbital (LUMO) of the electron acceptor. In addition, even the relative position of donor LUMO and acceptor LUMO is fundamental for an efficient charge transfer from the donor polymer to the acceptor fullerene. During the last years new polymers have been prepared and tested as donor materials in solar cells with the aim to improve the light absorption and the efficiency of the corresponding device; for each donor polymer is necessary to find a proper electron acceptor in order to maximize the Voc and to avoid losses in the electron transfer between donor and acceptor. In this chapter we briefly introduced the basic working principles of polymer solar cells (materials, device architecture, device physics, efficiency limits). Next we focused our attention on the properties of the most used electron acceptors, namely the fullerenes, and we implemented a theoretical approach to design fullerene derivatives to be used as electron acceptor in polymer solar cells. We calculated the LUMO levels of fullerene derivatives successfully used as electron acceptors and we correlated the obtained values with the Voc of the corresponding device. Furthermore, we investigated the possibility to tune the LUMO level varying the side group attached to the fullerene cage. © 2010 by Nova Science Publishers, Inc. All rights reserved.