James Orsini DVM, DipACVS, Hannah Galantino-Homer VMD, PhD and Christopher C. Pollitt BVSc, PhD Journal of Equine Veterinary Science February 2009 29 2 105-114 Systems theory is a way of describing complex and dynamic relationships. We applied systems theory to the structure and function of the equine foot in an effort to better understand laminitis and, in so doing, reconcile the various theories of its etiopathogenesis and find more universally effective preventive and therapeutic strategies. The foot is described as an open system, and its inherent vulnerabilities are explored. Cascade failure is discussed as a potentially unifying theory of laminitis. The fundamental failure in laminitis is failure of the lamellar dermal−epidermal bond, but that endpoint can be reached via vascular, enzymatic, inflammatory, or mechanical mechanisms, or any combination thereof. Inflammation is discussed as a common denominator, making anti-inflammatory therapy of greater importance than just pain management. Multimodal anti-inflammatory therapy is discussed, including selective COX-2 inhibitors, heparin, nutraceuticals, and inhibitors of matrix metalloproteinases (MMPs). Multimodal analgesic therapy also is important and may include nonsteroidal anti-inflammatory drugs (NSAIDs), opiates, epidural analgesics, physical therapy, relief of weight bearing, diligent nursing care, deep digital flexor tenotomy, and case-appropriate trimming and shoeing. Preventing laminitis still comes down to risk management: knowing the risk factors applicable to an individual horse and adjusting the management accordingly. Examples include weight management and control of carbohydrate intake in overweight horses and ponies, the use of pergolide in patients with pituitary pars intermedia dysfunction (PPID), and distal limb cryotherapy in high-risk patients. It is anticipated that application of molecular biologic techniques will further advance treatment and prevention of laminitis.