Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The improvement of knowledge about the pathogenetic mechanisms of JIA and advances in the understanding of pathways linking inflammation and autoimmunity and functions of multiple transcription factors have translated into new drug development for a tailored treatment directed to specific subpopulations of JIA patients.Areas covered: This review provides a digest of new investigational drugs which are currently or have been recently tested for treatment of JIA, and highlights some early phase clinical trials on rilonacept, givinostat, daclizumab, tofacitinib, and sarilumab.Expert opinion: Several studies have been focused on multiple complementary pathways driving synovial inflammation in JIA or molecules implicated in the inflammatory signature of JIA to deliver durable effects and prevent long-term complications. Since JIA is a complex disorder with multiple faces, identifying new treatment options for patients nonresponsive to the current drug armamentarium is of great relevance. A number of agents have been developed in the very last years, such as givinostat and tofacitinib, showing promising results in some cases, but trials remain in an early phase and few agents are currently under evaluation in a further phase setting. Longer-term use in possibly high numbers of patients and adequate data collection using large-scale registries are necessary to confirm clinical efficacy and provide a well-balanced overview of safety issues related to the drugs presented in this review.