Effective drug delivery is essential for the success of a medical treatment. Polymeric drug delivery systems (DDSs) are preferred over systemic administration of drugs due to their protection capacity, directed release, and reduced side effects. Among the numerous polymer sources, silks and recombinant silks have drawn significant attention over the past decade as DDSs. Native silk is produced from a variety of organisms, which are then used as sources or guides of genetic material for heterologous expression or engineered designs. Recombinant silks bear the outstanding properties of natural silk, such as processability in aqueous solution, self-assembly, drug loading capacity, drug stabilization/protection, and degradability, while incorporating specific properties beneficial for their success as DDS, such as monodispersity and tailored physicochemical properties. Moreover, the on-demand inclusion of sequences that customize the DDS for the specific application enhances efficiency. Often, inclusion of a drug into a DDS is achieved by simple mixing or diffusion and stabilized by non-specific molecular interactions; however, these interactions can be improved by the incorporation of drug-binding peptide sequences. In this review we provide an overview of native sources for silks and silk sequences, as well as the design and formulation of recombinant silk biomaterials as drug delivery systems in a variety of formats, such as films, hydrogels, porous sponges, or particles.