Current pharmacologic treatments for inflammatory diseases are largely palliative rather than curative. Most of them result in nonspecific immunosuppression. This can be associated with disruption of natural and induced immunity with significant, sometimes dramatic, adverse effects. Among the novel strategies that are under development, tools that target specific molecular pathways and cells, and more precisely modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a valuable class of therapeutic agents. They possess a number of intrinsic properties that are favorable for long-term treatments. They are also versatile components that can be modified to improve their capacities without affecting their bioactivity. Peptide-mediated immunotherapy has been evaluated in several appropriate experimental animal models. A few peptides are currently evaluated in clinical trials for the treatment of human chronic inflammatory diseases. In this review we describe a number of these emerging peptide therapeutics. We also discuss future challenges that, in addition to include selection of appropriate peptide drugs, also involve the optimization of peptide dosage and route of administration as well as the improvement of peptide stability for adequate bioavailability and specific targeting.