Interference Alignment (IA) has been widely recognized as a promising interference mitigation technique since it can achieve the optimal degrees of freedom in certain interference limited channels. In the context of Cognitive Radio (CR) networks, this technique allows the coexistence of two heterogeneous wireless systems in an underlay cognitive mode. The main concept behind this technique is the alignment of the interference on a signal subspace in such a way that it can be filtered out at the non-intended receiver by sacrificing some signal dimensions. This chapter starts with an overview of IA principle, Degree of Freedom (DoF) concept, and the classification of existing IA techniques. Furthermore, this chapter includes a discussion about IA applications in CR networks. Moreover, a generic system model is presented for allowing the coexistence of two heterogeneous networks using IA approach while relevant precoding and filtering processes are described. In addition, two important practical applications of the IA technique are presented along with the numerical results for underlay spectral coexistence of (i) femtocell-macrocell systems, and (ii) monobeam-multibeam satellite systems. More specifically, an uplink IA scheme is investigated in order to mitigate the interference of femtocell User Terminals (UTs) towards the macrocell Base Station (BS) in the spatial domain and the interference of multibeam satellite terminals towards the monobeam satellite in the frequency domain.