Atherosclerosis is the main underlying cause of cardiovascular disease and it is characterised by a chronic inflammatory process of the arterial wall. Monocytes, macrophages, lymphocytes and dendritic cells have been shown to play a key role in atherosclerotic plaque development. It is known that these cells establish direct intercellular communication through gap junction channels among themselves and with other cellular components of the arterial wall. These hexameric channels are constructed of connexins (Cx), their basic protein subunits. Differential expression of connexins within the arterial wall has been shown to be associated with specific stages of the development of atherosclerotic plaques both in mouse and human lesions. Reports derived from studies using animal models have recentlyrevealed opposite roles in inflammation leading to atherosclerosis for C×37 and C×43. We have also shown that different subsets of CD4 + T lymphocytes establish gap junctional communication with macrophages in vitro and that this interaction can be regulated by pro-atherogenic molecules such as oxidised-low density lipoproteins (oxLDL). Altogether, the evidence available demonstrates the importance of this type of intercellular cross talk in the pathophysiology of cardiovascular disease and provides new insights for understanding the mechanisms of its development.