Conditions affecting either or both extremities offer unique opportunities and challenges for investigators and clinicians. When the condition is purely unilateral, observations on the unaffected extremity may be used as a within-patient control, and thereby strengthen the ability to identify changes in the affected limb. However, such use presumes that the condition will not subsequently develop in the unaffected extremity. Bilateral presentations or subsequent development of disease in the unaffected extremity is common in conditions such as the carpal tunnel syndrome (CTS). Treatment of one extremity may lead to development or aggravation of CTS in the other extremity. Since both extremities may be necessary to perform certain activities, it can be difficult to clearly identify treatment effects when looking at functional outcomes. In an effort to avoid these complexities, investigators have used one of two approaches in studying CTS: either selecting only those patients with unilateral disease, or analyzing results by extremity, often avoiding any outcome measures that might depend upon both extremities (such as driving). We illustrate some of the shortcomings of this approach, such as loss of patients and data, with preliminary information from our ongoing prospective study of carpal tunnel surgery outcomes. We develop a dynamic model that incorporates etiologic factors and treatment effects to describe changes in CTS over time. This model accounts for extremity-specific and systemic factors, as well as possible interaction of the disease process in both hands. The advantages of this model include a more rational approach to research and care of extremity disorders, and research strategies which address a wider scope of patients and outcomes; however, its application is limited by the need for more extensive data collection.