Nicotine and nicotinic receptors have been explored for the past three decades as a strategy for pain control. These receptors are widely expressed throughout the central and peripheral nervous system as well as immune cells. Despite encouraging results with many selective alpha 4 beta 2* agonists in animal models of pain, human studies showed a narrow therapeutic window between analgesic efficacy and toxicity is associated with the use of these agonists as analgesics. alpha 4 beta 2 positive allosteric modulators are being developed with the aim to increase the potency or therapeutic window of these agonists. However, several recent developments have potentially opened new windows of opportunity in the use of nicotinic agents for analgesia. Accumulating evidences suggest that alpha 7 agonists and positive allosteric modulators hold a lot of promise in the treatment of chronic inflammatory pain conditions. In addition, recent animal studies suggest the therapeutic potential of ligands acting at other subtypes of nicotinic receptors. The current review will attempt to highlight these recent developments and outline some important findings that demonstrate further potential for the development of nicotinic ligands as novel analgesics.