This review considers the role of drug therapy in the treatment of post-stroke aphasia, the evidence for efficacy of different agents, and the theory-based explanations of drug-related benefits for aphasia rehabilitation. Pharmacological interventions modulating stroke-induced disruption of diverse neurotransmitters may improve language and communication deficits in aphasic patients through facilitation of brain plasticity and long-term potentiation. However, benefits are not evident for all compounds and refinement in clinical trial designs is required. Some pharmacological trials have failed because drug treatment was not combined with speech-language therapy, while other trials combining drugs with intensive model-driven therapies also failed probably because of short-trial duration, inadequate sample selection, or lack of drug action. Preliminary data reveals that combining neuroscience-based intensive aphasia techniques (constraint-induced aphasia therapy) and drugs acting on cholinergic and glutamatergic neurotransmitter systems are associated with better outcomes than other strategies and long-term maintenance of benefits. Although further studies are needed, current state of the evidence suggests that drug therapy may play a key role in the treatment of post-stroke aphasia.