Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO. •Studies in CNO have been “complicated” by the lack of case definitions, diagnostic modes of severity definition and outcomes.•Consensus was achieved among experts and patient representatives to inform and conduct CNO trials.•NSAID-refractory patients with mono- or multifocal CNO without complications should be enrolled.•Biological DMARDs promise potential and should be compared with pamidronate.•In addition to patient pain, outcomes should include physician global scores and MR imaging.