BackgroundPlacement of fillers in close proximity to the mimetic or sphincter muscles of the face appears to enhance or suppress muscle action in a relatively predictable way.MethodsFrom June 2016 to June 2021, patients who underwent the first author’s technique of myomodulation with dermal fillers to address aesthetic concerns or to manage facial spasms or synkinesis were evaluated in a retrospective case series. Additionally, the authors provide a technical guide for a whole-face approach to treatment with fillers and a conceptual map for treatment of each facial subunit with a focus on myomodulation.ResultsA total of 1352 patients (1108 women, 244 men; mean age, 51 years) underwent at least 1 treatment session during the 5-year study period. The treatment patterns of the study population and details of 2 representative cases are presented.ConclusionsAlthough not well understood mechanistically, myomodulation with injectable fillers shows promise for significant and reliable results of facial rejuvenation.Level of Evidence IVThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authorswww.springer.com/00266.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00266-022-03193-y.