Injectable controlled-release systems based on biodegradable copolymers of lactic and glycolic acids (PLGAs) have become widely used for delivery of protein therapeutics and vaccine antigens. Over the last five years, great strides have been made toward overcoming the difficulty of stabilizing PLGA-encapsulated proteins. In addition to stabilizing proteins during encapsulation with anhydrous methods, two approaches have proven highly effective to stabilize proteins during 1-month release incubation under physiological conditions: protein complexation with zinc and control of PLGA microclimate pH with antacid excipients. Described here are recent advances in the stabilization of proteins encapsulated in PLGA delivery systems.