The activation of NF-κB transcription factor is critical for a wide range of processes such as immunity, inflammation, cell development, growth and survival. It is activated by a variety of stimuli including cytokines, ionizing radiation and oxidative stress. Redox modulations of NF-κB pathway have been widely demonstrated. Studies carried out during last years have advanced our knowledge about possible connections between NF-κB pathway and the impact of free radicals. This review is an endeavor to gather recent results focused on this issue, although an important question, whether oxidative stress plays a physiological role in NF-κB activation, seems to be still unanswered.