In this review, we discuss the basic mechanisms of neural regeneration and repair and attempt to correlate findings from animal models of stroke recovery with clinical trials for aphasia. Several randomized controlled clinical trials involving manipulation of different neurotransmitter systems, including noradrenergic, dopaminergic, cholinergic, and glutamatergic systems, have shown signals of efficacy. Biological approaches such as anti-Nogo and cell replacement therapy have shown efficacy in preclinical models but have yet to reach proof of concept in the clinic. Finally, noninvasive cortical stimulation techniques have been used in a few small trials and have shown promising results. It appears that the efficacy of all these platforms can be potentiated through coupling with concomitant behavioral intervention. Given this array of potential mechanisms that exist to augment and/or stimulate neural reorganization after stroke, we are optimistic that approaches to aphasia therapy will transition from compensatory models to models in which brain reorganization is the goal.