The transcription factor NF-kappaB is a critical regulator of many cellular processes including cell survival and inflammation. NF-kappaB functions as a hetero- or homo-dimer which can be formed from five NF-kappaB subunits, NF-kappaB1 (p50 and its precursor p105), NF-kappaB2 (p52 and its precursor p100), RelA (p65), RelB and c-Rel. The most studied dimer is p50:p65, which is activated by the classical pathway and usually promotes gene expression. Activation of p50:p65 is linked with cell survival and promoting inflammation. This review provides a detailed overview of the structure, synthesis and function of the lesser characterised NF-kappaB subunit; NF-kappaB1 (p105 and p50). The diverse interactions of NF-kappaB1 with co-activators, co-repressors and other signaling networks that influence NF-kappaB1 gene expression are discussed. Finally the anti-inflammatory actions of NF-kappaB1 signaling will be assessed and the crucial need to design novel therapeutic drugs which exploit and amplify the anti-inflammatory actions of p50 will be explored.