Stroke is the leading cause of disability in older Americans. Each year 750,000 Americans suffer a stroke, two thirds of whom are left with neurological deficits that persistently impair function. Principal among them is hemiparetic gait that limits mobility and increases fall risk, promoting a sedentary lifestyle. These events propagate disability by physical deconditioning and "learned non-use," with further functional declines accelerated by the sarcopenia and fitness decrements of advancing age. Conventional rehabilitation care typically provides little or no structured therapeutic exercise beyond the subacute stroke recovery period, based on natural history studies showing little or no further functional motor recovery beyond 6 months after stroke. Emerging evidence suggests that new models of task-oriented exercise have the potential to improve motor function even years after stroke. This article presents treadmill as a task-oriented training paradigm to optimize locomotor relearning while eliciting cardiovascular conditioning in chronic stroke patients. Protocols for exercise testing and longitudinal aerobic training progression are presented that provide fundamental formulas that safely approach the complex task of customizing aerobic training to gait deficit severity in the high CVD risk stroke population. The beneficial effects of 6 months task-oriented treadmill exercise on cardiovascular-metabolic fitness, energy cost of hemiparetic gait, ADL mobility task performance, and leg strength are discussed with respect to the central and peripheral neuromuscular adaptations targeted by the training. Collectively, these findings constitute one initial experience in a much broader neuroscience and exercise rehabilitation development of task-oriented training paradigms that offer a multisystems approach to improving both neurological and cardiovascular health outcomes in the chronic stroke population.