This review describes the surface characterization of biodegradable poly(α-hydroxy acid)s (PAHA) microspheres used in pharmaceutics as controlled delivery systems and formulated via a complex process involving emulsification, solvent extraction, washing and freeze-drying By means of microscopy techniques (AFM and SEM) and wettability measurements, it was possible to precise the organization of the microsphere surface and to better explain the release profile of an entrapped model protein (bovine serum albumin). The analysis of the interfacial rheological behavior of the microsphere constituents at the liquid/liquid interface by means of a pendant drop method showed that the protein and the emulsifier strongly interpenetrated the PAHA interfacial layer. Finally, an interfacial model made of a PAHA monolayer spread at the air/water interface was proposed to study the hydrolytic degradation processes.