<p>Soft tissue injections have become one of the most commonly performed minimally invasive procedures in aesthetic medicine. Concomitant to the rapid rise in performed treatments, reports of vascular complications have increased, including skin necrosis, and in rare cases even irreversible vision loss. The common denominator of these complications is the underlying anatomy: the face contains a&#xa0;dense and highly variable network of arteries and veins, interconnected through multiple anastomoses, making the prediction of their course difficult. An in-depth understanding of vascular and layer-specific anatomy as well as regional “danger zones” is hence essential for the safe and effective use of fillers and other injectable treatments. This article highlights the vascular and layered anatomy of the face, region-specific injection strategies, and evidence-based principles for the prevention and management of vascular complications.</p>