textWhen aptamers emerged almost two decades ago, “selection-ologists” quickly realized the aptamer’s clinical potential - both as a diagnostic tool and as a therapeutic. Since that time, nearly hundreds of medically relevant targets have been successfully selected against. Moreover, many have proven efficacy in tissue culture and animal models. However, only one has successfully advanced to clinical use. Several key limitations in aptamer-based drugs may explain the dearth of aptamers in the pharmacy. Issues of expression level, delivery, and targeting will need to be addressed before aptamers can reach their full clinical potential. This work broaches on aspects of these limitations and leads into ways of transitioning the aptamer into clinical use.Cellular and Molecular Biolog