A primary goal of neurorehabilitation is to guide recovery of functional skills after injury through evidence-based interventions that operate to manipulate the sensorimotor environment of the client. While choice of intervention is an important decision for clinicians, we contend it is only one part of producing optimal activity-dependent neuroplastic changes. A key variable in the rehabilitation equation is engagement. Applying principles of engagement may yield greater neuroplastic changes and functional outcomes for clients. We review the principles of neuroplasticity and engagement and their potential linkage through concepts of attention and motivation and strategies such as mental practice and enriched environments. Clinical applications and challenges for enhancing engagement during rehabilitation are presented. Engagement strategies, such as building trust and rapport, motivational interviewing, enhancing the client education process, and interventions that empower clients, are reviewed. Well-controlled research is needed to test our theoretical framework and suggested outcomes. Clinicians may enhance engagement by investing time and energy in the growth and development of the therapeutic relationship with clients, as this is paramount to maintaining clients' investment in continuing therapy and also may act as a driver of neuroplastic changes.