Chronic pain continues to be a significant global burden despite the availability of a variety of non-pharmacologic and pharmacologic treatment options. Thus, there is a need for new analgesics with novel mechanisms of action. In this regard, antibodies directed against nerve growth factor (NGF-Abs) are a new class of agents in development for the treatment of chronic pain conditions such as osteoarthritis (OA) and chronic low back pain (CLBP). This comprehensive narrative review summarizes evidence supporting pro-nociceptive functions for NGF that include contributing to peripheral and central sensitization through tropomyosin receptor kinase A (TrkA) activation, and stimulation of local neuronal sprouting. The potential role of NGF in OA and CLBP pain signaling is also examined to provide a mechanistic basis for the observed efficacy of NGF-Abs in clinical trials of these particular pain states. Finally, the safety profile of NGF-Abs in terms of common adverse events, joint safety, and nerve structure/function is discussed.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.