Consensus exists on the importance of neural circuit in affecting the clinical outcome after sudden unexpected death in epilepsy (SUDEP). There is growing evidence that the serotonergic neuronal networks have a well-established role in SUDEP. Much progress has been made in our understanding of SUDEP since the seminal experiments of neural circuits. Future studies are that CeM-RVMM serotonergic circuits are poised to integrate multiple synaptic inputs from various sources thought to influence sudden unexpected death in epilepsy by melanocortinergic signaling.