The Academic Pediatric Association (APA, formerly the Ambulatory Pediatric Association) first encouraged multi-institutional collaborative research among its members over 30 years ago. Individual APA members subsequently went on to figure prominently in establishing formal research networks. These enduring collaborations have been established to conduct investigations in a variety of generalist contexts. At present, 4 generalist networks--Pediatric Research in Office Settings (PROS), the Pediatric Emergency Care Applied Research Network (PECARN), the COntinuity Research NETwork (CORNET), and Pediatric Research in Inpatient Settings (PRIS)--have a track record of extensive achievement in generating new knowledge aimed at improving the health and health care of children. This review details the history, accomplishments, and future directions of these networks and summarizes the common themes, strengths, challenges, and opportunities inherent in pediatric generalist network research.