New advances in biomaterial-based approaches to modulate the immune system are being applied to treat cancer, infectious diseases, and autoimmunity. Particulate systems are especially well-suited to deliver immunomodulatory factors to immune cells since their small size allows them to engage cell surface receptors or deliver cargo intracellularly after internalization. Biodegradable polymeric particles are a particularly versatile platform for the delivery of signals to the immune system because they can be easily surface-modified to target specific receptors and engineered to release encapsulated cargo in a precise, sustained manner. Micro- and nanoscale systems have been used to deliver a variety of therapeutic agents including monoclonal antibodies, peptides, and small molecule drugs that function to activate the immune system against cancer or infectious disease, or suppress the immune system to combat autoimmune diseases and transplant rejection. This review provides an overview of recent advances in the development of polymeric micro- and nanoparticulate systems for the presentation and delivery of immunomodulatory agents targeted to a variety of immune cell types including APCs, T cells, B cells, and NK cells.