With the abundance of low-cost storage devices, a plethora of applications that store and manage very large multi-dimensional trajectories (or time-series) datasets have emerged recently. Examples include traffic supervision systems, video surveillance applications, meteorology and more. Thus, it is becoming essential to provide a robust trajectory indexing framework designed especially for performing similarity queries in such applications. In this regard, this chapter presents an indexing scheme that can support a wide variety of (user-customizable) distance measures while, at the same time, it guarantees retrieval of similar trajectories with accuracy and efficiency.