Atrial fibrillation (AF) and sick sinus syndrome (SSS) are two conditions that frequently coexist. Despite a wealth of available knowledge, the link between these two entities is poorly understood. Whether AF is a harbinger of SSS or whether SSS predisposes to AF has been the subject of much debate. AF results in sinus node remodeling on a cellular and molecular basis that may promote SSS. However, not all patients with atrial fibrillation have SSS. Though “AF begets AF”, AF may also beget SSS; and SSS may also beget AF. Multiple studies have demonstrated that sinus node dysfunction may precede the onset of AF. This review will focus on alterations to sinus node structure and function, overdrive suppression, ion channel remodeling, and transient myocardial ischemia as possible mechanisms associated with AF induced SSS. In addition, we will review evidence suggesting that SSS, characterized by a combination of atrial extrasystoles, dispersion of excitability recovery and sinus node ischemia, may lead to AF. Additional factors common to both conditions such as aging and interstitial atrial fibrosis, may explain their coexistence. All this raises many therapeutic challenges associated with the interplay of AF and SSS.