The multidimensional issue of pain in relation to the need for efficient treatment has been the focus of extensive research. Gaining insight into the molecular mechanisms of pain and identifying specific genes and proteins as possible drug targets is strongly required considering that not all patients can be adequately treated with the currently available drugs. This up-to-date review aimed to summarize the findings of recent proteomic and genomic approaches in different types of pain to comment on their potential role in pain signaling pathways and to evaluate their possible contribution to the development of novel and possibly more targeted pain therapeutic strategies. Although pain treatment strategies have been greatly improved during the past century, no ideal targeted pain treatment has been developed. The development of modern and accurate platforms of technology for the study of genetics and physiology of pain has led to the identification of an increased number of altered genes and proteins that are involved in pain-related pathways. Through genomics and proteomics, pain-related genes and proteins, respectively, may be identified as diagnostic markers or drug targets improving therapeutic strategies. Furthermore, such molecular mediators of pain may reveal novel strategies for individualized pain management. The utilization of unique experimental approaches (through specific animal models) as well as powered genetic association studies conducted on appropriate populations is more than essential.