The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PID) including Severe Combined Immune Deficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PID in multicenter longitudinal retrospective, prospective and cross-sectional studies. Since 2009, participating centers have enrolled over 800 subjects on PIDTC protocols for SCID, and enrollment on the studies in WAS and CGD is underway. Four pilot projects have been funded and 12 junior investigators have received fellowship awards. Important publications of the consortium describe outcomes of hematopoietic cell transplantation (HCT) for SCID during 2000–2009, diagnostic criteria for SCID, and the pilot project of newborn screening (NBS) for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups and international colleagues. Funded by the NIAID and ORDR, NCATS, the PIDTC has recently received renewal for another 5 years. Here, we review accomplishments of the group, projects underway, highlights of recent workshops and challenges for the future.