Vaso-occlusive (VOC) episodes represent the major source of morbidity and impairment for patients with sickle cell disease (SCD), and the management of pain is a continued challenge to patients, families, and health care providers. There is little consensus among medical care providers about the optimal pharmacological and non-pharmacological approaches to SCD pain management. In addition, VOC episodes and its medical management can produce physiological and pharmacological sequelae which can be detrimental to the patients. Conversely, optimal management of the VOC episodes is likely to have short-term as well as long term benefits of the patient. This program consists of three integrated clinical research studies which address the optimal management of VOC episodes from psychological, pharmacological and physiological perspectives. The three specific aims of this project are: 1) to conduct a randomized clinical trial to test the efficacy of a family-based pain management program designed to teach pediatric patients with SCD and their primary caregivers how to optimally control pain by using a combination of pharmacological and non-pharmacological strategies; 2) to conduct a double-blind randomized clinical trial to determine the benefits and risks of adjuvant use of methylphenidate in the treatment of severe VOC pain in hospitalized patients; and 3) to conduct a randomized trail of the outpatient use of the incentive spirometer during vaso-occlusive episodes to determine if its use this setting will prevent the development of the acute chest syndrome (ACS).