Resistant hypertension is frequently encountered and remains challenging in everyday clinical practice despite the availability of numerous effective antihypertensive drugs. Existing limitations in drug therapy renders renal nerve ablation (RNA) an attractive alternative for the management of resistant hypertension. RNA has been proven so far both effective and safe in small clinical studies. However, every novel technique raises several questions that need to be answered before the wide application of this approach. Likewise, existing data with RNA leave some unanswered questions, which among others include: the heterogeneity in blood pressure response, the identification of response predictors, the extent of RNA, the association between office and ambulatory blood pressure reduction, the long-term efficacy and safety of the procedure, the time-course of blood pressure response, and the effects on renal function in the long-term. This review aims to discuss these issues since RNA represents one of the hottest topics in hypertension and research directions are urgently needed.