The purpose of this study was to review the clinical course of reported hypersensitivity reactions associated with use of soft tissue fillers and the response of these reactions to treatment. In this comprehensive literature review, we identified ~40 published reports that together reported numerous adverse reactions associated with use of nonpermanent soft tissue fillers; however, very few of these reactions were consistent with type I immediate or type IV delayed hypersensitivity reactions. Based on their clinical course and response to treatment, most reported hypersensitivity reactions are likely due to an infectious process. Although there are no confirmed reports of biofilm reactions associated with nonpermanent fillers, the possibility of bacterial contaminants should be considered in acute or chronic inflammatory reactions associated with use of nonpermanent soft tissue fillers. Early treatment with antibiotics is recommended.