Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease characterised by small joint swelling, deformity, and dysfunction. Its exact aetiology is unclear. Current treatment approaches do not control harmful autoimmune attacks or prevent irreversible damage without considerable side effects. Nicotinamide adenine dinucleotide (NAD+), an important hydrogen carrier in mitochondrial respiration and oxidative phosphorylation, is the major determinant of redox state in the cell. NAD+ metabolites act as degradation substrates for a wide range of enzymes, such as sirtuins, poly-ADP-ribose polymerases, ADP-ribosyltransferases, and CD38. The roles of NAD+ have expanded beyond its role as a coenzyme, linking cellular metabolism to inflammation signalling and immune response. The aim of this review is to illustrate the role of NAD+-related enzymes in the pathogenesis of RA and highlight the potential therapeutic role of NAD+ in RA.