Multimodal analgesia is commonplace in effective management of complex pain. Opiate-based medications, despite their efficacy, carry risks of addiction, tolerance, and adverse side effects, which has encouraged the exploration of non-opiate based analgesia. The following chapter provides an overview of non-opiate analgesics used in urology, with a particular focus on gabapentinoids and tricyclic antidepressants. Despite their initial development for other indications, their complex mechanisms of action allow them to modulate sensory signals and pain, providing relief in chronic pelvic pain, interstitial cystitis and overactive bladder. However, their use requires careful consideration of pharmacokinetics, potential side effects, and the need for ongoing monitoring to ensure adequate patient safety during long-term treatment.