Chronic osteomyelitis is refractory to nonsurgical treatment due to a resilient, infective nidus that harbors sessile, matrix-protected pathogens bound to substrate surfaces within the wound. Curative treatment mandates physical (surgical) removal of the biofilm colony, adjunctive use of antibiotics to eliminate residual phenotypes, and efforts to optimize the host response throughout therapy. Patient selection, therapeutic options, and the treatment format are determined by the Cierny/Mader staging system, while reconstruction is governed by the integrity/stability of the affected bone(s) and quality/quantity parameters of the soft-tissue envelope.