Poly(beta-amino ester) (abbreviated as PBAE or PAE) refers to a polymer synthesized from an acrylate and an amine by Michael addition and has properties inherent to tertiary amines and esters, such as pH responsiveness and biodegradability. The versatility of building blocks provides a library of polymers with miscellaneous physicochemical and mechanical properties. When used alone or together with other materials, PBAEs can be fabricated into different formulations in order to fulfill various requirements in drug delivery (for instance, gene, anticancer drugs, and antimicrobials delivery) and natural complex mimicry (nanochaperones). This progress report discusses the recent developments in design, synthesis, formulations, and applications of PBAEs in biomedical fields and provides a perspective view for the future of the PBAEs.