With the advent of the genomic revolution and the sequencing of the human genome complete, the majority of pharmaceuticals under development are proteins. Consequently, new techniques to more effectively administer these new protein therapeutics need to be developed. One method that is gaining popularity in the research community involves the use of responsive hydrogel actuators for flow control in drug delivery devices. Responsive hydrogels are materials able to undergo a volume change in response to a stimulus from their local environment. The following paper overviews recent advances made using hydrogel actuators for flow control such as resistance based valves, hydrogel jacket valves, hybrid hydrogel membrane valve, electrically triggered valves, and biomimetic valves. Also reviewed are several hydrogel flow control systems such as a flow sorter and pH-regulation system. The chemistry of the hydrogel actuators can be tweaked to allow physiological variables to trigger the volume expansion of the hydrogel actuators as demonstrated by several glucose sensitive hydrogel valves reviewed below. Therefore, the door to physiological feedback controlling the infusion rate in a drug delivery device is opened and has the potential to revolutionize protein pharmaceutical drug delivery.