Immune regulatory pathways involving the newly discovered T regulatory (Treg) and Th17 cells are amongst the principal targets of immunosuppressive agents employed in transplant recipients and key mediators of host inflammatory responses in fungal infections. These novel signaling pathways, in concert with or independent of Th1/Th2 responses, have potentially important implications for yielding valuable insights into the pathogenesis of immune reconstitution syndrome (IRS) in transplant recipients, for aiding the diagnosis of this entity, and for achieving a balance of immune responses that enhance host immunity while curbing unfettered inflammation in IRS.