Medication nonadherence is a prevalent public health issue that contributes to significant medical costs and detrimental health outcomes. This is especially true in patients with hypercholesterolemia, a condition affecting millions of American adults and one that is associated with increased risk for coronary and cerebrovascular events. Considering the magnitude of outcomes related to this disease, the medical community has placed significant emphasis on addressing the treatment for high cholesterol, and progress has been made in recent years. However, poor adherence to therapy continues to plague health outcomes and more must be understood and done to address suboptimal medication taking. Here we provide an overview of the reasons for poor medication adherence in patients with hypercholesterolemia and describe recent efforts to curb nonadherence. Suggested approaches for improving medication taking in patients with high cholesterol are also provided to guide practitioners, patients, and payers.