There is a universal agreement that when lifestyle modifications are inadequate to control the hyperglycemia, metformin should be considered the first line of pharmacological therapy. However, when metformin monotherapy fails, there is no consensus as to which drug should be added. Many new classes of drugs that are currently available including DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors have undergone cardiovascular outcome trials which had been made mandatory by the regulatory authority and thereby established their cardiovascular safety or at least neutrality. Though sulfonylureas are one of the widely prescribed drugs both in developed and developing countries and have proven their efficacy for glycemic control and prevention of microvascular complications, there is considerable uncertainty about its cardiovascular safety which has been going on for nearly five decades. In this review, we will critically analyze the efficacy and cardiovascular safety of sulphonylureas, based on the latest available literature to clarify their role in our day-to-day clinical practice.