<p>Polyarticular-course juvenile idiopathic arthritis (polyJIA) is a chronic inflammatory arthritis involving &gt; 4 distinct joints over the course of the disease. PolyJIA tends to be more difficult to treat than other forms of nonsystemic JIA, but advances in immunosuppressive therapies over the past 25 years have dramatically reduced patient morbidity. Despite significant advances in treatment options and outcomes, there is little evidence to guide how and when these treatments should be implemented to be most effective. Optimizing the initial timing and choice of these medications may further enhance outcomes and potentially mitigate the need for serial trials of therapy. There are recent data to suggest that earlier and more aggressive initial immunosuppressive therapy may help patients with polyJIA achieve inactive disease more quickly and may improve long-term outcomes. This approach, however, is counterweighted by the risk of overtreatment and the need for improved risk stratification models that can reliably inform individualized treatment strategies. This article explores the main treatment approaches to new-onset polyJIA and current evidence to support which approach may be optimal.</p>