Children with special health care needs (CSHCN) use relatively high quantities of healthcare resources and have overall higher morbidity than the general pediatric population. Embedding clinical pharmacists into the Patient-Centered Medical Home (PCMH) to provide comprehensive medication management (CMM) through collaborative practice agreements (CPAs) for children, especially for CSHCN, can improve outcomes, enhance the experience of care for families, and reduce the cost of care. Potential network infrastructures for collaborative practice focused on CSHCN populations, common language and terminology for CMM, and clinical pharmacist workforce estimates are provided. Applying the results from the CMM in Primary Care grant, this paper outlines the following: (1) setting up collaborative practices for CMM between clinical pharmacists and pediatricians (primary care pediatricians and sub-specialties, such as pediatric clinical pharmacology); (2) proposing various models, organizational structures, design requirements, and shared electronic health record (EHR) needs; and (3) outlining consistent documentation of CMM by clinical pharmacists in CSHCN populations.