Every day, in clinics and hospitals around the world, occupational therapists care for patients with serious problems requiring viable solutions. Each patient is unique, and his or her problem does not necessarily correspond to existing practice models. Practitioners must adapt standard approaches to provide effective outcomes, yet problems exist for which few or no beneficial approaches have been identified. Such clinical issues require solutions to be generated de novo from the practitioner’s body of knowledge and past experience. Yet, no single new intervention can be used without prior validation of its efficacy. Only a therapist with a prepared mind can accept such challenges, recognize what is known and not yet known, design studies to acquire that needed knowledge, and translate it into successful clinical treatment strategies. The occupational therapist with a prepared mind is one willing to seize unexpected opportunities and construct new paradigms of practice. Innovation through scientific inquiry requires a prepared mind.