Functional deficits frequently persist after ischemic stroke despite reperfusion therapies and rehabilitation. They impair autonomy and quality of life, highlighting the need for complementary strategies. Several pharmacological approaches have been evaluated to enhance post-stroke recovery, including selective serotonin reuptake inhibitors, levodopa, and amphetamines. Clinical trials have shown limited functional benefits and safety concerns. These findings illustrate the gap between biological plausibility and clinical efficacy. Mechanistic approaches targeting brain plasticity, such as blockade of the C-C chemokine receptor type 5, have shown promising results in preclinical models and could potentiate the effects of rehabilitation.