Retention devices and methods are provided for drug delivery. The device may include a housing configured for intraluminal deployment into a human or animal subject and at least one reservoir contained within the housing. The at least one reservoir may have an actuation end and a release end and contain at least one drug formulation. A plug may be contained within the at least one reservoir and be moveable from the actuation end toward the release end. The device may also include an actuation system operably connected to the actuation end of the at least one reservoir and configured to drive the at least one drug formulation from the reservoir. The device may also include at least one retention member affixed to the housing and movable between a non-stressed position, a deployment position, and a retention position for retaining the device in an intraluminal location in the subject.