Histrionicotoxins are potent neurotoxic compounds isolated from the skin secretions of marine cone snails, particularly species belonging to the genus *Conus*. These toxins exhibit high selectivity for voltage-gated sodium channels (VGSCs) and can modulate neuronal excitability by blocking these channels. They are classified into several subfamilies based on their primary structures and functional properties, with each type displaying distinct pharmacological activities. For instance, Conotoxin *Hii.1a* is known to inhibit the activation of VGSCs at high concentrations, while other members may induce rapid depolarization or block the channels in a different manner. The application of histrionicotoxins in neurobiology and pharmacology has been significant due to their potential as lead compounds for developing novel analgesics and local anesthetics. Researchers are actively investigating these toxins to understand their mechanisms at the molecular level, aiming to exploit their unique properties for therapeutic purposes.