A medication adherence system for and method of facilitating an automated adherence program is disclosed. The medication adherence system of the present disclosure may be, for example, a web-based and / or telephone-based system by which enrolled participants may access the automated adherence program. The medication adherence system may utilize an adherence application for assessing patients with respect to, for example, certain barriers and / or other adherence issues. Additionally, by use of adherence application, the content of the interactions between patients and the medication adherence system as well as the frequency and timing of the interactions is optimized with respect to the drop-off periods of medications. The adherence application may include, for example, an interactions routine for processing interactions content, a user interface, a feedback component, a drop-off algorithm, a patient assessment component that may further include a revealed barriers algorithm and a derived barriers algorithm. Further, the medication adherence system of the present disclosure provides a reporting mechanism.