End-of-life (EOL) is a term used to indicate that a product has completed its service lifetime and has reached the end of its useful life. A number of reasons can cause the product to complete its service life time including deterioration or obsolescence. Deterioration implies that the performance and hence the reliability of the product has significantly lessened making it no longer suitable for use due to disintegration or degeneration. Obsolescence is often used to describe the products that are rendered invalid due to systemic, functional, and style mismatch or due to notification of expiration. Lack of deterioration implies that the obsolete products are likely to preserve their functionality. The duration of shelf life varies due to numerous product-specific factors for each product. Prescription drugs, a major product class in drugs and pharmaceuticals, are one product category that is likely to complete its service life time prior to deterioration. The gap between the shelf life and the actual obsolescence date leads to storage or disposal of growing number of EOL pharmaceutical products. This fact, coupled with the significant hazard potential of these products require a well-established reverse logistics system capable of handling EOL operations such as take back, reuse, recycle, and proper disposal of these products. With these motivations, this study proposes a reverse logistics framework that embodies environmental, economical, and physical concerns for EOL pharmaceutical products. An radio frequency identification-based information technology infrastructure for the proposed system along with a comprehensive overview of the existing drug take-back regulations worldwide is also provided.