Knowledge of variable anatomy is key for excellent outcomes from the administration of botulinum toxin for aesthetic purposes. One must understand the location and function of each facial muscle to predict the patient's desired outcome. One concept often overlooked by injectors is the understanding of the target muscle's depth. In addition, a firm understanding of where each facial muscle originates and attaches can be essential to correctly identifying and injecting the correct muscle with botulinum toxin. Facial muscles often overlap each other and cross various planes. For example, an injector may be unaware that the corrugator supercilii muscle lies in different depths medially and laterally. Novice injectors may miss the variability of this muscle and inject the lower frontalis muscle by mistake. This may lead to a heavy brow look, or it could drop the area between the brows, creating an appearance of anger. This article explores a three-dimensional anatomical approach to achieve excellent outcomes, rather than the two-dimensional approach traditionally discussed. Many of the injection techniques defined in this article are considered off-label by the Food and Drug Administration at the time of this publication but are commonly discussed in peer-reviewed literature and consensus opinion reports. Twelve facial muscles often injected for positive aesthetic outcomes will be outlined as well as seven facial muscles to generally avoid.