The nuclear factor κB (NF‐κB) transcription factor family plays a key role in regulation of the inflammatory pathway in response to different physiological stimuli starting from development to ageing. The dysregulation of NF‐κB has been associated with many pathological conditions like inflammatory diseases, neurodegeneration, metabolic diseases and various kinds of malignancies. The NF‐κB pathway is regulated by number of post‐translational modifications, including phosphorylation and ubiquitination. Ubiquitin (Ub) E3 ligases are key regulators of the process of ubiquitination and provide specificity to the pathway as they recognise the substrate and determine the topology of ubiquitination. TRIMs, members of RING family of Ub E3 ligases, are characterised by the presence of three conserved domains, RING, B‐Box and coiled‐coil (RBCC). Emerging evidence suggests that TRIMs regulate innate immune signalling during infection and different pathological conditions. The studies have demonstrated the role of TRIMs in regulation of inflammatory pathways including NF‐κB. Recent reports suggest that TRIMs play a critical role in regulation of the NF‐κB pathway by ubiquitinating proteins at different steps. In the current review, we discuss the role of TRIMs as novel NF‐κB regulators and their role in different pathophysiological conditions.