Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a clinically available osteoinductive growth factor. In its current form, approved for clinical use, however, the growth factor is delivered in excessively high doses, resulting in unpredictable bone growth and unwanted, sometimes life-threatening, clinical side effects. It has clearly been demonstrated that the sustained, long-term release of the proteins can lead to improved ossification, owing particularly to the rapid metabolism of the biologically active growth factor when delivered alone in solution. Delivery systems for rhBMP-2 have been investigated extensively; yet still, further exploration into the best means of protein delivery — in order to curb the side effect profile and improve the quality of the bone generated — is warranted. The present review of literature introduces extensive work evaluating optimal rhBMP-2 delivery, with particular focus on natural polymers, inorganic materials, as well as synthetic materials. In particular, poly(DL-lactide-co-glycolide) (PLGA) microspheres, conventionally fabricated by a solvent extraction/evaporation procedure, are discussed for their use in sustained drug delivery. The application of rhBMP-2 for bone tissue engineering holds great promise for researchers and clinicians in both the medical and dental fields; yet, there remains a need for further investigation into improved protein delivery mechanisms.