The discipline of medicine is truly a combination of both science and art, and nowhere is this more true than in the practice of differential diagnosis. From the initial clinic visit, when the patient presents with a nonspecific symptom, until the final treatment is rendered, the clinician must constantly and critically evaluate his or her diagnosis. This process can be expedited by using a consistent and comprehensive methodology that reminds the clinician to entertain the full spectrum of causes. Two such methodologies have been presented in this article. It is important, however, to note that the systems presented here are by no means the sole, or even best, methods. The clinician should experiment and discover what works best for him or her. Any system is ideal if it allows the clinician to consistently derive the correct diagnosis in a short amount of time. After all, the most important part of any treatment is the proper diagnosis.