In this paper, we consider the conditions under which a given ensemble of two-qubit states can be optimally distinguished by local operations and classical communication (LOCC). We begin by completing the perfect distinguishability problem of two-qubit ensembles - both for separable operations and LOCC - by providing necessary and sufficient conditions for the perfect discrimination of one pure and one mixed state. Then, for the well-known task of minimum error discrimination, it is shown that almost all two-qubit ensembles consisting of three pure states cannot be optimally discriminated using LOCC. This is surprising considering that any two pure states can be distinguished optimally by LOCC. Special attention is given to ensembles that l...