The plant-derived secondary metabolites have, over the years, greatly contributed to our current understanding of the important mechanisms related to the process of pain transmission and treatment. Furthermore, they have permitted us to characterise receptor types and identify endogenous ligands involved in the mechanism of nociception. In this review, we discuss the recent advances that have occurred regarding plant-derived substances in the process of development of new analgesic drugs. Plants, such as Papaver somniferum, Cannabis sativa and those of the Capsicum and Salix species, have greatly accounted for the development of clinically relevant drugs which are useful for the management of pain disorders. The recent advances in our understanding of the mechanisms of action of the above plant-derived substances, together with use of molecular biology techniques, have greatly accelerated attempts to identify promising targets for the discovery of new, safe and efficient analgesic drugs. Despite the great progress which has occurred in the elucidation of pain transmission and despite decades of use, leaving aside its known undesirable sides effects, morphine continues to be one of the most used drugs in clinical practice for the treatment of pain disorders. Thus, safer and more efficacious analgesic drugs are urgently needed. A search through the literature reveals that many potentially active antinociceptive plant-derived compounds have been identified. However, studies aiming to investigate their cellular and molecular mechanisms of action and well-controlled clinical trials to prove their efficacy in humans are still lacking. Nevertheless, natural or synthetic substances that bind to vanilloid or cannabinoid receptors, or even those that are capable of modulating the endogenous ligands which bind to these receptors, are expected to soon appear to assist in the treatment of several pain disorders, including those of neuropathic or neurogenic origin.