Cocaine-associated stroke (CAS) is an important cause of disability, especially among younger adults. Improved management has increased survival but little has been discussed about rehabilitation, including medication management. Therefore, experience and therapeutic drug management are described during inpatient rehabilitation with three patients with CAS. Case 14 is a 50-year-old male with a history of hypertension who presented with right hemiparesis, aphasia and depression. He was treated with paroxetine for depression and bromocriptine for poor initiation with a good response, improving by 50 FIM points in 44 days. Case 2 is a 44 year-old female with quadriparesis, aphasia, and deficits in attention and initiation. Methylphenidate for attention deficits and bromocriptine for poor initiation was associated with an excellent functional gain (50 FIM points in 37 days). She eventually returned to work. Case 3 is a 46-year-old female with a history of hypertension who presented with right hemiparesis, aphasia and depression. Without neuropharmacologic intervention, she gained 35 FIM points during an uneventful 47 day rehabilitation stay. Acutely, cocaine can induce cerebral vasoconstriction, cerebrovascular spasm, cerebral vasculitis and intracerebral haemorrhage. Chronic use depletes and destroys dopaminergic pathways, which may be a major factor in depression, and attention and initiation deficits-all observed in these cases. Generally, rapid improvements were seen in mood and cognition in two cases where medication was used. Based on the current literature and pathophysiology of CAS, it is suggested that trials of dopaminergic agents for cognition and extremely cautious use of buproprion for depression may be warrented. Details of the above cases and the practical and theoretical issues of neuropharmacologic intervention in CAS are discussed.