The myriad pathologies leading to and resulting from atrial fibrillation (AF) have led to many theories regarding how substrate should be defined and how to reconcile substrate ablation with trigger ablation. The identification of spatiotemporally stable areas of very low amplitude short cycle length (CL) complex fractionated atrial electrograms (CFAEs) in a sea of otherwise discrete normal amplitude and relatively longer CL electrograms led to ablate the CFAEs as markers of abnormal substrate. This pure substrate-based ablation strategy has resulted in remarkable success with great benefit including stroke and mortality reduction in high-risk patients with very long standing persistent AF. However, these findings have not been consistently replicated by others. In this review, we discuss the prevailing mechanisms underlying CFAEs, how to map and ablate CFAE sites, correlation of CFAE areas to those of ganglionic plexi, clinical outcomes of the approach, and the controversy surrounding targeting CFAEs as substrate sites for AF ablation.