Infectious diseases of synovial and hoof structures in horses can be devastating to soundness and can result in life-threatening complications. Timely diagnosis and early aggressive treatment can result in successful outcomes and resumption of athletic careers; however, delays in recognition and therapy can be the most costly reasons for failure. Sterilization of affected compartments and tissues requires removal of microorganisms and compromised tissue. Debridement, lavage, and appropriate antimicrobial drug use are the most reliable avenues of treatment. Antimicrobial drugs can be administered by local, regional, and systemic routes. Lavage techniques and debridement typically require surgical manipulations.