Local anaesthesia is commonly employed prior to most dental procedures. It is imperative to understand the mechanisms by which local anaesthetics work, so that their efficacy can be improved for painless dental care. Local anaesthesia also has major clinical implications in that it can precipitate emergencies in patients with an underlying systemic disease. It is imperative that a dentist have a thorough knowledge of the considerations one must take when administering local anaesthesia in patients with systemic diseases. This review discusses the various methods of enhancing the efficacy of local anaesthetics and the precautionary measures one must take when administering local anaesthesia in medically compromised patients.