As research on the efficacy or effectiveness of interventions to improve motor functioning in cerebral palsy (CP) has accumulated and been incorporated into systematic reviews, the foundation for evidence-based practice in CP is growing. To determine whether an intervention is effective, clinical trials report mean group differences. However, even if a statistically significant mean group effect is found, this does not imply that this intervention was effective for each study participant or ensure positive outcomes for all with CP. A personalized approach to medical care is currently being advocated based primarily on increasingly recognized genetic variations in individual responses to medications and other therapies. A similar approach is also warranted, and perhaps more justifiable, in CP which includes a heterogeneous group of disorders. Even interventions deemed highly effective in CP demonstrate a range of individual responses along a continuum from a negative or negligible response to a strong positive effect, the bases for which remain incompletely understood. This narrative review recommends that the next critical step in advancing evidence-based practice is to implement research strategies to identify patient factors that predict treatment responses so we can not only answer the question ‘what works’, but also ‘what works best, for whom’.