Chronic pain remains a major problem worldwide, despite the availability of various non-pharmacological and pharmacological treatment options. Therefore, new analgesics with novel mechanisms of action are needed. Monoclonal antibodies (mAbs) are directed against specific, targeted molecules involved in pain signaling and processing pathways that look to be very effective and promising as a novel therapy in pain management. Thus, there are mAbs against tumor necrosis factor (TNF), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), or interleukin-6 (IL-6), among others, which are already recommended in the treatment of chronic pain conditions such as osteoarthritis, chronic lower back pain, migraine, or rheumatoid arthritis that are under preclinical research. This narrative review summarizes the preclinical and clinical evidence supporting the use of these agents in the treatment of chronic pain.