This chapter explores immune-mediated complications associated with dermal fillers from a rheumatologist’s perspective. With the increasing use of fillers—particularly hyaluronic acid—adverse reactions have also risen. These range from local inflammation and delayed hypersensitivity to systemic autoimmune responses triggered by the adjuvant properties of filler substances. Early complications include angioedema, infections, and non-inflammatory nodules, while delayed reactions often involve foreign body granulomas. Treatment strategies depend on the type, timing, and etiology of the reaction. Therapeutic approaches include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and a range of immunosuppressive agents such as methotrexate, hydroxychloroquine, cyclosporine, and tacrolimus. In more resistant cases, biologics like anti-tumor necrosis factor (TNF) agents or Janus Kinase (JAK) inhibitors (e.g., tofacitinib) have shown promise. Despite various therapeutic options, a standardized and evidence-based approach is still lacking. This highlights the need for further research to optimize management protocols and reduce the morbidity associated with filler-induced immune complications.