Stroke is a leading cause of disability among older adults and more than half of stroke survivors have some residual neurological impairment. Traditionally, managing the aftermath of stroke has been by the implementation of several physical and language therapy modalities. The limitations of these rehabilitation efforts have sparked an interest in finding other ways to enhance neurological recovery. Some of these novel approaches have included pharmacological interventions, cell-derived treatments, and cortical magnetic stimulation. Mounting evidence over the last 2 decades suggests that pharmacological manipulations may have the potential to modulate practice-dependent neuroplasticity and potentially improve neurological recovery after stroke. Multiple pharmacological agents with different mechanisms of action have been evaluated, showing conflicting results. Some studies suggest some promise, yet the quality of the available studies is suboptimal overall, with most of the studies being underpowered. So far, the most promising agents include the antidepressants for motor recovery and acetylcholinesterase inhibitors and memantine for aphasia. However, large, well-designed clinical trials are needed to address the shortcomings of the available data and before any pharmacological agent can be recommended for routine use as part of the standard algorithm of stroke management.