Injectable or implantable drug delivery systems providing on-demand ultrasound-triggered drug release and methods for controlling the release of drug in a patient are provided herein. The on-demand drug delivery systems contain a drug depot and a drug encapsulated in an encapsulating material, where the encapsulating material is different from the depot. In the preferred embodiment, the depot also contains microbubbles that encapsulate one or more gases. The microbubbles enhance the drug release when ultrasound is applied compared to the same system in the absence of microbubbles. In a preferred embodiment, the drug delivery system, contains an encapsulating material, preferably liposomes, a drug to be delivered, microbubbles, and at least two hydrogel-forming precursor components. Following injection or implantation, the patient can control the time, location and dosage released by administering ultrasound.