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This chapter aims to review the current pharmacological options for neuropathic pain treatment, their mechanisms of action, and future directions for clinical practice. Achieving pain relief in neuropathic pain conditions remains a challenge in clinical practice. The field of pharmacotherapy for neuropathic pain has encountered significant difficulties in translating substantial advances in our understanding of the underlying pathophysiological mechanisms into clinically effective therapies. This chapter presents the drugs recommended for the pharmacotherapy of neuropathic pain, based on the widely accepted treatment guidelines formulated by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain. In addition to discussing how the evidence base is created as part of international consortia, the drugs are also examined in terms of their putative molecular mechanisms as well as pharmacological pleiotropy, i.e., their potential unspecific and multi-target effects resulting in modulation of neuronal hyperexcitability. The chapter closes with a discussion of potential future developments in the field.