Poly(aspartic acid) (PASP) is an anionic polypeptide that is a highly versatile, biocompatible, and biodegradable polymer that fulfils key requirements for use in a wide variety of biomedical applications. The derivatives of PASP can be readily tailored via the amine-reactive precursor, poly(succinimide) (PSI), which opens up a large window of opportunity for the design and development of novel biomaterials. PASP also has a strong affinity with calcium ions, resulting in complexation, which has been exploited for bone targeting and biomineralization. In addition, recent studies have further verified the biocompatibility and biodegradability of PASP-based polymers, which is attributed to their protein-like structure. In light of growing interest in PASP and its derivatives, this paper presents a comprehensive review on their synthesis, characterization, modification, biodegradation, biocompatibility, and applications in biomedical areas.