Effective drug delivery requires the precise spatial and temporal delivery of therapeutic agents to the target site. To this end, a variety of chemical and physicochemical approaches have been devised to create lipid vesicles (liposomes) that can be triggered to release their contents in a controlled fashion. The triggers include changes in pH, redox potential, temperature, or the level of specific enzymes. We review the chemistries that have recently been applied to exploit the pH and redox potential triggers so as to release vesicle contents in the appropriate biological location.