In recent years, many stimuli-triggered drug delivery platforms have been designed to deliver drugs accurately to specific sites and reduce their side effects, improving “on-demand” therapeutic efficacy. Adenosine-5′-triphosphate (ATP)-responsive drug delivery methods are examples of these systems that use ATP molecules as a trigger for delivery of therapeutic agents. Since intra- and extra-cellular ATP concentrations are significantly different from each other (1-10 mM and <0.4 mM, respectively), the use of ATP can be a practical method for regulating drug release. Aptamers possess unique properties including, ligand-specific response, short sequence (~ 20-80 bases) and easy functionalization. Thus, their combination with ATP-responsive systems results in more accurate drug delivery systems and greater control of drug release. A wide range of nanoparticles, such as polymeric nanogels, liposomes, metallic nanoparticles, protein, or DNA nano-assemblies, have been employed in the fabrication of nanocarriers. In this review, we describe several ATP-responsive drug delivery systems based on the various carriers and discuss the challenges and strengths of each method.