This review focuses on the presentation of the diagnostic and therapeutic principles for treatment of chronic osteomyelitis of long bones in adults. Early detection of the offending bacteria is a crucial step which has to be performed with tissue and fluids from the depth of the wound. Superficial samples and swaps from fistulas should be avoided and are not considered to be representative. Chronic osteomyelitis is characterized by necrotic and nonvascularized bony tissue which represents one of the most relevant sources for recurrence infection. Appropriate therapy includes radical excision of the diseased bone and infected scar tissue, closure of the wound with well-vascularized (muscle) flaps, stabilization, and administration of adequate antibiotics.