Various local anesthetics have been explored for spinal anesthesia, falling into two primary categories: esters and amides. Initial investigations focused on esters like cocaine and amylocaine. However, amylocaine is no longer used in clinical practice. Procaine, known as Novocain, was synthesized and saw research into its intrathecal use. Procaine gained popularity due to its presumed systemic effects and concerns over the neurotoxicity of spinal cocaine administration. Notably, procaine's side effects often include nausea, vasomotor paralysis, and an elevated risk of anaphylaxis due to its metabolite para aminobenzoic acid (PABA). Subsequently, bupivacaine, an intermediate to long-acting amide local anesthetic, was discovered, synthesized, and widely applied clinically. Concerns about potential toxicity led to research on two (S)-enantiomers of bupivacaine for spinal anesthesia. Initial studies on spinal ropivacaine (the S-enantiomer of bupivacaine) were conducted. Further investigations into the other pure (S)-enantiomer of bupivacaine, levobupivacaine, began. Intrathecal administration of both levobupivacaine and ropivacaine continues to be explored. After chloroprocaine's approval, mepivacaine and prilocaine were introduced for spinal anesthesia. Both of these medications, also xylidine derivatives, displayed similar potency to lidocaine. However, due to concerns about transient neurologic symptoms associated with intrathecal lidocaine administration, mepivacaine and prilocaine are being further investigated as alternatives for ambulatory or short to moderate duration surgeries