Interstitial cystitis (IC) is a chronic symptom-complex characterized by pathological sensation of the bladder (i.e. bladder pain in addition to augmented sensory signals such as urinary frequency and urgency) without evidence of bacterial cystitis or other identifiable lower urinary tract disease. Patients with IC typically describe feeling the urge to void frequently, as well as pain in the bladder and/or urethra. The painful sensation may be described as burning, pressure, sharp, or aching, and is often difficult for the patient to localize precisely. Multiple theories as to the cause of IC have been proposed with varying degrees of evidence. The current body of literature supports the idea that IC is associated with an intrinsic pathology of the bladder urothelial cells. The identification and complete characterization of antiproliferative factor (APF), which is uniquely expressed by urothelial cells in bladders affected by IC, are major advances in the understanding of IC. Additionally, urothelial cells have been likened to neurons because of their ability to express neuronal receptors and release neurotransmitters. The purinergic pathway has been shown to be upregulated in urothelial cells in bladders affected by IC. These new findings should help to direct the development of newer clinical treatments for IC. A complete understanding of IC will only be possible with parallel advances in both basic and clinical sciences.